{"entity": "researcher", "timestamp": "2026-08-10T19:24:01.939Z", "family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "affiliations": ["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.", "Department of Radiation Oncology, University of California, San Francisco, San Francisco, California."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9"}}, "publications": [{"entity": "publication", "iuid": "22f6e10d4d60441a86a092b4ca737121", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/22f6e10d4d60441a86a092b4ca737121.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/22f6e10d4d60441a86a092b4ca737121"}}, "title": "Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer", "authors": [{"family": "Moreno-Rodriguez", "given": "Thaidy", "initials": "T", "orcid": "0000-0003-3588-3889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be9adfae1d354f85a76d66de8bc08cba.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Pasam", "given": "Anupama", "initials": "A"}, {"family": "Chan", "given": "Joanna", "initials": "J"}, {"family": "Devereux", "given": "Lisa", "initials": "L"}, {"family": "Foye", "given": "Adam", "initials": "A", "orcid": "0000-0002-9910-9836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74c8c402b4a243ab95b9d20ecc43d4b9.json"}}, {"family": "Zhu", "given": "Xiaolin", "initials": "X", "orcid": "0000-0002-3221-595X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9.json"}}, {"family": "Weinstein", "given": "Alana S", "initials": "AS", "orcid": "0000-0002-1563-9072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e16ba4d459704a96adc34a85197bab05.json"}}, {"family": "Trigos", "given": "Anna S", "initials": "AS"}, {"family": "Wyatt", "given": "Alexander W", "initials": "AW", "orcid": "0000-0003-2399-0329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41e8ef800a344c68be341f0691438260.json"}}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Dehm", "given": "Scott M", "initials": "SM", "orcid": "0000-0002-7827-5579", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb947d721b424bb190ddf41a808a2cb0.json"}}, {"family": "Bootsma", "given": "Matthew L", "initials": "ML"}, {"family": "Zhao", "given": "Shuang G", "initials": "SG", "orcid": "0000-0002-9166-6507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7d9e7e456be4376adb63a3e5ab895a7.json"}}, {"family": "Lupien", "given": "Mathieu", "initials": "M", "orcid": "0000-0003-0929-9478", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1967a3e4d1ff43998c93ea10d874cd01.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}, {"family": "Sandhu", "given": "Shahneen", "initials": "S"}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}], "type": "journal-article", "published": "2026-04-15", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "issn-l": "1474-7596", "volume": "27", "issue": "1", "pages": null}, "abstract": "Targeted therapy prolongs the lives of men with metastatic castration-resistant prostate cancer (mCRPC) but mCRPC is ultimately lethal. DNA copy gains that amplify the Androgen Receptor (AR) gene locus are a key driver of resistance to targeted therapy in mCRPC. Our group has recently shown that extra-chromosomal DNA (ecDNA) frequently drives this amplification. We hypothesized that ecDNA and other complex structural variants (cSVs) also affect other established drivers of therapy resistance in mCRPC and continue to evolve over time. To test this hypothesis, we reconstructed cSV profiles in 193 mCRPC tumors using whole genome and transcriptome sequencing, with matched Hi-C data for 77 tumors.\n\nWe identify ecDNA in more than half of mCRPC biopsies and show it frequently amplifies driver genes such as AR and MYC and their non-coding enhancers. The presence of ecDNA is significantly associated with whole genome doubling, chromothripsis, and inactivating TP53 alterations. Deep sequencing analysis of 53 rapid autopsy samples shows cSVs amplifying AR can arise independently within distinct tumors in a single patient. Phylogenetic analysis of tumor evolution implicates this cSV as an early event during metastatic spread. Additionally, a paired analysis of mCRPC samples as patients developed resistance to AR pathway inhibitor (ARPI) therapy demonstrates cSVs evolve in response to ARPI and can be detected in both tumor tissue and circulating tumor DNA.\n\nWe conclude that cSVs, particularly ecDNA, are a pervasive contributor to intra-patient heterogeneity in late-stage mCRPC and a key driver of targeted therapy resistance.", "doi": "10.1186/s13059-026-04074-2", "pmid": "41987223", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC13191960"}, {"db": "pii", "key": "10.1186/s13059-026-04074-2"}], "notes": [], "created": "2026-04-15T19:30:46.855Z", "modified": "2026-07-06T20:08:37.710Z"}, {"entity": "publication", "iuid": "cb64d786281d480d984052947db110c2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cb64d786281d480d984052947db110c2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cb64d786281d480d984052947db110c2"}}, "title": "Androgen receptor splice variant 7 expression levels distinguish AR-mutated from nonmutated metastatic castration-resistant prostate cancers", "authors": [{"family": "Paschalis", "given": "Alec", "initials": "A", "orcid": "0000-0001-9566-5096", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/de1cf8539acd4ec3a8cad39b966ccaa1.json"}}, {"family": "Figueiredo", "given": "Ines", "initials": "I"}, {"family": "Bogdan", "given": "Denisa", "initials": "D", "orcid": "0000-0002-3017-4832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/960fd8ea3ce143559ebaff1149a59ea3.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Santos", "given": "Rita", "initials": "R"}, {"family": "Gurel", "given": "Bora", "initials": "B", "orcid": "0000-0002-5018-8078", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c0ed82612d614c16b45a528515cfba94.json"}}, {"family": "Taha", "given": "Tarek", "initials": "T"}, {"family": "Longoria", "given": "Ossian", "initials": "O"}, {"family": "Ferreira", "given": "Ana", "initials": "A"}, {"family": "Bertan", "given": "Claudia", "initials": "C"}, {"family": "Brittain", "given": "Nicholas", "initials": "N"}, {"family": "Nelson", "given": "Ryan", "initials": "R"}, {"family": "Walker", "given": "Laura", "initials": "L"}, {"family": "Neeb", "given": "Antje", "initials": "A", "orcid": "0000-0002-6516-2938", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6529e261d8be4c33878b9cf8d399632d.json"}}, {"family": "Welti", "given": "Jonathan", "initials": "J"}, {"family": "Yuan", "given": "Wei", "initials": "W"}, {"family": "Mitsopoulos", "given": "Costas", "initials": "C"}, {"family": "Plymate", "given": "Stephen R", "initials": "SR"}, {"family": "Haffner", "given": "Michael C", "initials": "MC", "orcid": "0000-0003-0809-6425", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cce395fe9a8b4fcdaec08d5d1cb37dde.json"}}, {"family": "Sowalsky", "given": "Adam G", "initials": "AG", "orcid": "0000-0003-2760-1853", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3692960b43fa4971b3b05958abeb12ce.json"}}, {"family": "Carreira", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-5077-5379", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9a1f9e675b844e93928caec267794b80.json"}}, {"family": "Sharp", "given": "Adam", "initials": "A", "orcid": "0000-0002-3740-1612", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/25a4df1796a54c66ace14e632a239cd7.json"}}, {"family": "Gaughan", "given": "Luke", "initials": "L"}, {"family": "de Bono", "given": "Johann", "initials": "J", "orcid": "0000-0002-2034-595X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22ac727724ef47b591c0f0bc2285adcc.json"}}], "type": "journal-article", "published": "2026-04-01", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "issn-l": "0021-9738", "volume": "136", "issue": "7", "pages": null}, "abstract": "New androgen receptor (AR) pathway inhibitors (ARPIs) in clinical development, including AR degraders and CYP11A inhibitors, largely target ligand-dependent AR activation and have reported antitumor activity in metastatic castration-resistant prostate cancer (mCRPC) resistant to established ARPIs, predominately against tumors with AR mutations. We hypothesized that AR-mutated mCRPC exhibits lower AR splice variant 7 (AR-V7) expression and remains full-length-AR (FL-AR) driven, explaining, in part, the antitumor activity of these AR ligand-binding domain (LBD) targeting drugs. The data herein demonstrate that mCRPC tissue biopsies with detectable AR mutations express significantly lower levels of AR-V7 protein and associate with better overall survival and enhanced sensitivity to ARPIs. This is independent of differences in the total number of global splicing events but may be related to differences in splicing factor expression between AR-mutated and nonmutated mCRPC. In conclusion, AR-mutated mCRPC frequently exhibits low AR-V7 expression, arguably explaining the enhanced sensitivity to ARPIs observed in these cancers. Consequently, AR mutation status may serve as a biomarker to predict response to AR-directed therapies.", "doi": "10.1172/jci198193", "pmid": "41919503", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC13038193"}, {"db": "pii", "key": "198193"}], "notes": "Authorship note: AP, IF, DB, and AL are co\u2013first authors.", "created": "2026-04-02T07:53:43.865Z", "modified": "2026-07-10T08:28:48.410Z"}, {"entity": "publication", "iuid": "97db9245561b4895816a8a5c19b7ce9d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/97db9245561b4895816a8a5c19b7ce9d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/97db9245561b4895816a8a5c19b7ce9d"}}, "title": "Early gonadotoxic effects of cyclophosphamide on the prepubertal testis and the feasibility of reducing toxicity through combined antioxidant therapy", "authors": [{"family": "Eskafinoghani", "given": "Amirhesam", "initials": "A", "orcid": "0000-0002-9717-4810", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/870acfdb0dcb4f978107a194d485df9f.json"}}, {"family": "Palomares", "given": "Arturo Reyes", "initials": "AR"}, {"family": "Hao", "given": "Xia", "initials": "X"}, {"family": "Mohammadi", "given": "Roudabeh", "initials": "R"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Rodriguez-Walberg", "given": "Kenny A", "initials": "KA", "orcid": "0000-0003-4378-6181", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab738f3602664a20bb1db36e55156d8b.json"}}], "type": "journal-article", "published": "2026-03-00", "journal": {"title": "Reprod. Toxicol.", "issn": "0890-6238", "pages": "109156", "volume": "140", "issn-l": null}, "abstract": "Early chemotherapy-induced gonad toxicity threatens future fertility in boys, yet early in-vivo testicular responses are poorly defined. To characterize acute effects of cyclophosphamide (CPA) on the prepubertal testis and explore whether combined antioxidants (AO; L-carnitine [LC] and N-acetyl cysteine [NAC]) modulate these changes. CBA/B6 F1 male pups (postnatal day 7-9) were randomized to saline control, CPA (100 mg/kg i.p.), AO, or CPA+AO. Testes were collected every 8 h to 48 h for histology/immunostaining and were pooled (n = 3 per group/time point) for bulk RNA-seq per group/time point. Histology showed emerging degeneration from \u223c32 h with prominent effects by 48 h after CPA, including reduced germ cell layers, increased \u03b3H2AX/CC3, and decreased Ki67. Transcriptionally, CPA perturbed apoptosis/developmental pathways as early as 16 h, preceding overt histological change. AO and CPA+AO groups displayed partial transcriptional shifts toward control profiles, consistent with mitigation of CPA-associated signatures, but not full normalization. In neonatal mouse testis, CPA elicits rapid transcriptomic reprogramming within 16 h, before morphological injury at \u223c32-48 h. Concomitant AO shows preliminary, partial protective transcriptional effects. These proof-of-concept data support transcriptomics as an early, sensitive readout of testicular toxicity and motivate follow-up studies with independent validation and long-term outcomes prior to clinical translation.", "doi": "10.1016/j.reprotox.2025.109156", "pmid": "41475676", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pii", "key": "S0890-6238(25)00327-2"}], "notes": [], "created": "2026-01-03T12:14:31.089Z", "modified": "2026-07-10T08:29:04.493Z"}, {"entity": "publication", "iuid": "72fb93708492426787e659dd3bc5fdc7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/72fb93708492426787e659dd3bc5fdc7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/72fb93708492426787e659dd3bc5fdc7"}}, "title": "Early gonadotoxic effects of cyclophosphamide on the prepubertal testis and the feasibility of reducing toxicity through combined antioxidant therapy", "authors": [{"family": "Eskafinoghani", "given": "Amirhesam", "initials": "A", "orcid": "0000-0002-9717-4810", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/870acfdb0dcb4f978107a194d485df9f.json"}}, {"family": "Reyes Palomares", "given": "Arturo", "initials": "A"}, {"family": "Hao", "given": "Xia", "initials": "X"}, {"family": "Mohammadi", "given": "Roudabeh", "initials": "R"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Rodriguez-Walberg", "given": "Kenny A", "initials": "KA", "orcid": "0000-0003-4378-6181", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab738f3602664a20bb1db36e55156d8b.json"}}], "type": "posted-content", "published": "2025-03-19", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.03.18.643799", "pmid": null, "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [], "notes": [], "created": "2026-04-18T06:33:10.419Z", "modified": "2026-04-18T06:33:10.438Z"}, {"entity": "publication", "iuid": "1d81ac07fdfe4adea0206e44bfcb3c82", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1d81ac07fdfe4adea0206e44bfcb3c82.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1d81ac07fdfe4adea0206e44bfcb3c82"}}, "title": "Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer.", "authors": [{"family": "Chesner", "given": "Lisa N", "initials": "LN", "orcid": "0009-0007-2779-8824", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ee8b85578474244893baffac823a58c.json"}}, {"family": "Polesso", "given": "Fanny", "initials": "F", "orcid": "0000-0003-1245-4563", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9484fee75b2d441c8510ae30ce37a272.json"}}, {"family": "Graff", "given": "Julie N", "initials": "JN", "orcid": "0000-0002-5708-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/68744986932f498190374291f1be9120.json"}}, {"family": "Hawley", "given": "Jessica E", "initials": "JE", "orcid": "0000-0003-1720-5654", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b6b6ee79b0f4e93bcb9f71be1d9730a.json"}}, {"family": "Smith", "given": "Alexis K", "initials": "AK", "orcid": "0009-0000-7291-0714", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a9df1bdb7834a37a5b2fac5e777bb40.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Das", "given": "Rajdeep", "initials": "R", "orcid": "0000-0001-9280-6076", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0db3bc4e3a6f4580afdf4e40e8898afb.json"}}, {"family": "Shenoy", "given": "Tanushree", "initials": "T", "orcid": "0000-0003-0653-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1698244d836246a390d3b097ffe74200.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Zhao", "given": "Faming", "initials": "F", "orcid": "0000-0002-8238-3863", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e0a0cfc04ae4b539a943cee62ca20ab.json"}}, {"family": "Hu", "given": "Ya-Mei", "initials": "YM", "orcid": "0000-0002-2575-1770", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ba1af89b3fe240078c10ee9fd29ce106.json"}}, {"family": "Linder", "given": "Simon", "initials": "S", "orcid": "0000-0002-3315-305X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d63b10a5f739402eb504c0283e12374e.json"}}, {"family": "Chen", "given": "William S", "initials": "WS", "orcid": "0000-0002-3717-670X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d9d15aafb919408989cb2fc513aa5e81.json"}}, {"family": "Hawkins", "given": "Reed M", "initials": "RM", "orcid": "0000-0001-8611-2588", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea0ebd971af64162885b9e396fbc6713.json"}}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Zhu", "given": "Xiaolin", "initials": "X", "orcid": "0000-0002-3221-595X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9.json"}}, {"family": "Foye", "given": "Adam", "initials": "A", "orcid": "0000-0002-9910-9836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74c8c402b4a243ab95b9d20ecc43d4b9.json"}}, {"family": "Li", "given": "Haolong", "initials": "H", "orcid": "0000-0002-8628-9698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbc2d2abba854008b56d417e6083614c.json"}}, {"family": "Kim", "given": "Lisa M", "initials": "LM", "orcid": "0000-0002-2071-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/979df3fb1c77411f946d134c551bfd81.json"}}, {"family": "Bhalla", "given": "Megha", "initials": "M", "orcid": "0009-0009-3380-624X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21acd3ee63f3474aa7bc99b046611c5e.json"}}, {"family": "O'loughlin", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4783-2352", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8398b9a487c6475ca7a33ef536772de6.json"}}, {"family": "Kuzuoglu-Ozturk", "given": "Duygu", "initials": "D", "orcid": "0000-0003-1737-5020", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f63b95d881143ed895f178c6f64777d.json"}}, {"family": "Hua", "given": "Junjie T", "initials": "JT", "orcid": "0000-0002-1197-1174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac6c246ec5104f86a2eae545eb2a8155.json"}}, {"family": "Badura", "given": "Michelle L", "initials": "ML", "orcid": "0000-0001-5325-8097", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e13cf11cc85841e482605117504afc84.json"}}, {"family": "Wilkinson", "given": "Scott", "initials": "S", "orcid": "0000-0002-2613-8425", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0da3b827b89e4ba2b657361b8c334b7a.json"}}, {"family": "Trostel", "given": "Shana Y", "initials": "SY", "orcid": "0000-0002-5929-2576", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/da389d5148774df887b14c50c51d5919.json"}}, {"family": "Bergman", "given": "Andries M", "initials": "AM", "orcid": "0000-0001-5223-2549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87e541c17883471b9bbc1a78f7fe40e3.json"}}, {"family": "Ruggero", "given": "Davide", "initials": "D", "orcid": "0000-0002-9444-5865", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1bc649dd2c24244940b160635756d15.json"}}, {"family": "Drake", "given": "Charles G", "initials": "CG", "orcid": "0000-0001-9610-3677", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a9e88dc6ce042c4b2fc14c779555952.json"}}, {"family": "Sowalsky", "given": "Adam G", "initials": "AG", "orcid": "0000-0003-2760-1853", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3692960b43fa4971b3b05958abeb12ce.json"}}, {"family": "Fong", "given": "Lawrence", "initials": "L", "orcid": "0000-0002-6428-428X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0124854879b543d8b9653fd99cce332c.json"}}, {"family": "Cooperberg", "given": "Matthew R", "initials": "MR", "orcid": "0000-0003-4339-6685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7035b6815b824338a8ca67f3c23f9923.json"}}, {"family": "Zwart", "given": "Wilbert", "initials": "W", "orcid": "0000-0002-9823-7289", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/014603af06df4629b83fb3e7aa17710a.json"}}, {"family": "Guan", "given": "Xiangnan", "initials": "X", "orcid": "0009-0003-4978-3093", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac038dc1ab0b476ca8b02f34777af03e.json"}}, {"family": "Ashworth", "given": "Alan", "initials": "A", "orcid": "0000-0003-1446-7878", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/217e8097b1a14deba9247b30c1b978a7.json"}}, {"family": "Xia", "given": "Zheng", "initials": "Z", "orcid": "0000-0003-3364-8324", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29699b2527c145fd91d53ce77d3ba590.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}, {"family": "Gilbert", "given": "Luke A", "initials": "LA", "orcid": "0000-0001-5854-0825", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cc47a939f85b4a668bb091d77e2e330c.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}, {"family": "Moran", "given": "Amy E", "initials": "AE", "orcid": "0000-0003-1952-7737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/724dca05212a4607acb6151bc9884efe.json"}}], "type": "journal article", "published": "2025-03-03", "journal": {"title": "Cancer Discov", "issn": "2159-8290", "issn-l": "2159-8274", "volume": "15", "issue": "3", "pages": "481-494"}, "abstract": "Immunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients.", "doi": "10.1158/2159-8290.CD-24-0559", "pmid": "39652470", "labels": {"Arian Lundberg": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC11873725"}, {"db": "pii", "key": "750492"}], "notes": [], "created": "2025-03-20T14:05:18.677Z", "modified": "2025-11-14T07:49:59.126Z"}, {"entity": "publication", "iuid": "b5cb34f60b154d46943268cc516c2cec", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b5cb34f60b154d46943268cc516c2cec.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b5cb34f60b154d46943268cc516c2cec"}}, "title": "Elucidating acquired PARP inhibitor resistance in advanced prostate cancer.", "authors": [{"family": "Seed", "given": "George", "initials": "G"}, {"family": "Beije", "given": "Nick", "initials": "N"}, {"family": "Yuan", "given": "Wei", "initials": "W"}, {"family": "Bertan", "given": "Claudia", "initials": "C"}, {"family": "Goodall", "given": "Jane", "initials": "J"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Tyler", "given": "Matthew", "initials": "M"}, {"family": "Figueiredo", "given": "Ines", "initials": "I"}, {"family": "Pereira", "given": "Rita", "initials": "R"}, {"family": "Baker", "given": "Chloe", "initials": "C"}, {"family": "Bogdan", "given": "Denisa", "initials": "D"}, {"family": "Gallagher", "given": "Lewis", "initials": "L"}, {"family": "Cieslik", "given": "Jan-Phillipp", "initials": "JP"}, {"family": "Greening", "given": "Semini", "initials": "S"}, {"family": "Lambros", "given": "Maryou", "initials": "M"}, {"family": "Neves", "given": "Rui", "initials": "R"}, {"family": "Magraner-Pardo", "given": "Lorena", "initials": "L"}, {"family": "Fowler", "given": "Gemma", "initials": "G"}, {"family": "Ebbs", "given": "Berni", "initials": "B"}, {"family": "Miranda", "given": "Susana", "initials": "S"}, {"family": "Flohr", "given": "Penny", "initials": "P"}, {"family": "Bianchini", "given": "Diletta", "initials": "D"}, {"family": "Rescigno", "given": "Pasquale", "initials": "P"}, {"family": "Porta", "given": "Nuria", "initials": "N"}, {"family": "Hall", "given": "Emma", "initials": "E"}, {"family": "Gurel", "given": "Bora", "initials": "B"}, {"family": "Tunariu", "given": "Nina", "initials": "N"}, {"family": "Sharp", "given": "Adam", "initials": "A"}, {"family": "Pettit", "given": "Stephen", "initials": "S"}, {"family": "Stoecklein", "given": "Nikolas H", "initials": "NH"}, {"family": "Sandhu", "given": "Shahneen", "initials": "S"}, {"family": "Quigley", "given": "David", "initials": "D"}, {"family": "Lord", "given": "Christopher J", "initials": "CJ"}, {"family": "Mateo", "given": "Joaquin", "initials": "J"}, {"family": "Carreira", "given": "Suzanne", "initials": "S"}, {"family": "de Bono", "given": "Johann", "initials": "J"}], "type": "journal article", "published": "2024-12-09", "journal": {"title": "Cancer Cell", "issn": "1878-3686", "volume": "42", "issue": "12", "pages": "2113-2123.e4", "issn-l": "1535-6108"}, "abstract": "PARP inhibition (PARPi) has anti-tumor activity against castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) defects. However, mechanisms underlying PARPi resistance are not fully understood. While acquired mutations restoring BRCA genes are well documented, their clinical relevance, frequency, and mechanism of generation remain unclear. Moreover, how resistance emerges in BRCA2 homozygously deleted (HomDel) CRPC is unknown. Evaluating samples from patients with metastatic CRPC treated in the TOPARP-B trial, we identify reversion mutations in most BRCA2/PALB2-mutated tumors (79%) by end of treatment. Among reversions mediated by frameshift deletions, 60% are flanked by DNA microhomologies, implicating POLQ-mediated repair. The number of reversions and time of their detection associate with radiological progression-free survival and overall survival (p < 0.01). For BRCA2 HomDels, selection for rare subclones without BRCA2-HomDel is observed following PARPi, confirmed by single circulating-tumor-cell genomics, biopsy fluorescence in situ hybridization (FISH), and RNAish. These data support the need for restored HRR function in PARPi resistance.", "doi": "10.1016/j.ccell.2024.10.015", "pmid": "39577422", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "EMS207307"}, {"db": "pmc", "key": "PMC7618010"}, {"db": "pii", "key": "S1535-6108(24)00403-3"}], "notes": [], "created": "2025-11-14T07:48:35.081Z", "modified": "2026-01-03T12:41:34.396Z"}, {"entity": "publication", "iuid": "3e3149ba56534f57be85c69020b838aa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3e3149ba56534f57be85c69020b838aa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3e3149ba56534f57be85c69020b838aa"}}, "title": "Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.", "authors": [{"family": "Cal\u00ec", "given": "Bianca", "initials": "B"}, {"family": "Troiani", "given": "Martina", "initials": "M"}, {"family": "Bressan", "given": "Silvia", "initials": "S"}, {"family": "Attanasio", "given": "Giuseppe", "initials": "G"}, {"family": "Merler", "given": "Sara", "initials": "S"}, {"family": "Moscarda", "given": "Viola", "initials": "V"}, {"family": "Mosole", "given": "Simone", "initials": "S"}, {"family": "Ricci", "given": "Elena", "initials": "E"}, {"family": "Guo", "given": "Christina", "initials": "C"}, {"family": "Yuan", "given": "Wei", "initials": "W"}, {"family": "Gallagher", "given": "Lewis", "initials": "L"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Bernett", "given": "Ilona", "initials": "I"}, {"family": "Figueiredo", "given": "Ines", "initials": "I"}, {"family": "Arzola", "given": "Rydell Alvarez", "initials": "RA"}, {"family": "Abreut", "given": "Ernesto Bermudez", "initials": "EB"}, {"family": "D'Ambrosio", "given": "Mariantonietta", "initials": "M"}, {"family": "Bancaro", "given": "Nicol\u00f2", "initials": "N"}, {"family": "Brina", "given": "Daniela", "initials": "D"}, {"family": "Zumerle", "given": "Sara", "initials": "S"}, {"family": "Pasquini", "given": "Emiliano", "initials": "E"}, {"family": "Maddalena", "given": "Martino", "initials": "M"}, {"family": "Lai", "given": "Ping", "initials": "P"}, {"family": "Colucci", "given": "Manuel", "initials": "M"}, {"family": "Pernigoni", "given": "Nicol\u00f2", "initials": "N"}, {"family": "Rinaldi", "given": "Andrea", "initials": "A"}, {"family": "Minardi", "given": "Davide", "initials": "D"}, {"family": "Morlacco", "given": "Alessandro", "initials": "A"}, {"family": "Moro", "given": "Fabrizio Dal", "initials": "FD"}, {"family": "Sabbadin", "given": "Marianna", "initials": "M"}, {"family": "Galuppini", "given": "Francesca", "initials": "F"}, {"family": "Fassan", "given": "Matteo", "initials": "M"}, {"family": "R\u00fcschoff", "given": "Jan Hendrik", "initials": "JH"}, {"family": "Moch", "given": "Holger", "initials": "H"}, {"family": "Rescigno", "given": "Pasquale", "initials": "P"}, {"family": "Francini", "given": "Edoardo", "initials": "E"}, {"family": "Saieva", "given": "Calogero", "initials": "C"}, {"family": "Modesti", "given": "Mikol", "initials": "M"}, {"family": "Theurillat", "given": "Jean-Philippe", "initials": "JP"}, {"family": "Gillessen", "given": "Silke", "initials": "S"}, {"family": "Wilgenbus", "given": "Petra", "initials": "P"}, {"family": "Graf", "given": "Claudine", "initials": "C"}, {"family": "Ruf", "given": "Wolfram", "initials": "W"}, {"family": "de Bono", "given": "Johann", "initials": "J"}, {"family": "Alimonti", "given": "Andrea", "initials": "A"}], "type": "journal article", "published": "2024-10-14", "journal": {"title": "Cancer Cell", "issn": "1878-3686", "volume": "42", "issue": "10", "pages": "1676-1692.e11", "issn-l": "1535-6108"}, "abstract": "Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.", "doi": "10.1016/j.ccell.2024.08.018", "pmid": "39303726", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pii", "key": "S1535-6108(24)00317-9"}], "notes": [], "created": "2025-11-14T07:48:48.647Z", "modified": "2026-01-03T12:41:52.036Z"}, {"entity": "publication", "iuid": "66598865387641aabc6f82b3fa85c7f5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/66598865387641aabc6f82b3fa85c7f5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/66598865387641aabc6f82b3fa85c7f5"}}, "title": "BCL2 expression is enriched in advanced prostate cancer with features of lineage plasticity.", "authors": [{"family": "Westaby", "given": "Daniel", "initials": "D"}, {"family": "Jim\u00e9nez-Vacas", "given": "Juan M", "initials": "JM"}, {"family": "Figueiredo", "given": "Ines", "initials": "I"}, {"family": "Rekowski", "given": "Jan", "initials": "J"}, {"family": "Pettinger", "given": "Claire", "initials": "C"}, {"family": "Gurel", "given": "Bora", "initials": "B"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Bogdan", "given": "Denisa", "initials": "D"}, {"family": "Buroni", "given": "Lorenzo", "initials": "L"}, {"family": "Neeb", "given": "Antje", "initials": "A"}, {"family": "Padilha", "given": "Ana", "initials": "A"}, {"family": "Taylor", "given": "Joe", "initials": "J"}, {"family": "Zeng", "given": "Wanting", "initials": "W"}, {"family": "Das", "given": "Souvik", "initials": "S"}, {"family": "Hobern", "given": "Emily", "initials": "E"}, {"family": "Riisnaes", "given": "Ruth", "initials": "R"}, {"family": "Crespo", "given": "Mateus", "initials": "M"}, {"family": "Miranda", "given": "Susana", "initials": "S"}, {"family": "Ferreira", "given": "Ana", "initials": "A"}, {"family": "Hanratty", "given": "Brian P", "initials": "BP"}, {"family": "Nava Rodrigues", "given": "Daniel", "initials": "D"}, {"family": "Bertan", "given": "Claudia", "initials": "C"}, {"family": "Seed", "given": "George", "initials": "G"}, {"family": "Fenor de La Maza", "given": "Maria de Los Dolores", "initials": "MLD"}, {"family": "Guo", "given": "Christina", "initials": "C"}, {"family": "Carmichael", "given": "Juliet", "initials": "J"}, {"family": "Grochot", "given": "Rafael", "initials": "R"}, {"family": "Chandran", "given": "Khobe", "initials": "K"}, {"family": "Stavridi", "given": "Anastasia", "initials": "A"}, {"family": "Varkaris", "given": "Andreas", "initials": "A"}, {"family": "Stylianou", "given": "Nataly", "initials": "N"}, {"family": "Hollier", "given": "Brett G", "initials": "BG"}, {"family": "Tunariu", "given": "Nina", "initials": "N"}, {"family": "Balk", "given": "Steven P", "initials": "SP"}, {"family": "Carreira", "given": "Suzanne", "initials": "S"}, {"family": "Yuan", "given": "Wei", "initials": "W"}, {"family": "Nelson", "given": "Peter S", "initials": "PS"}, {"family": "Corey", "given": "Eva", "initials": "E"}, {"family": "Haffner", "given": "Michael", "initials": "M"}, {"family": "de Bono", "given": "Johann", "initials": "J"}, {"family": "Sharp", "given": "Adam", "initials": "A"}], "type": "journal article", "published": "2024-09-17", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "134", "issue": "18", "issn-l": "0021-9738"}, "abstract": "The widespread use of potent androgen receptor signaling inhibitors (ARSIs) has led to an increasing emergence of AR-independent castration-resistant prostate cancer (CRPC), typically driven by loss of AR expression, lineage plasticity, and transformation to prostate cancers (PCs) that exhibit phenotypes of neuroendocrine or basal-like cells. The anti-apoptotic protein BCL2 is upregulated in neuroendocrine cancers and may be a therapeutic target for this aggressive PC disease subset. There is an unmet clinical need, therefore, to clinically characterize BCL2 expression in metastatic CRPC (mCRPC), determine its association with AR expression, uncover its mechanisms of regulation, and evaluate BCL2 as a therapeutic target and/or biomarker with clinical utility. Here, using multiple PC biopsy cohorts and models, we demonstrate that BCL2 expression is enriched in AR-negative mCRPC, associating with shorter overall survival and resistance to ARSIs. Moreover, high BCL2 expression associates with lineage plasticity features and neuroendocrine marker positivity. We provide evidence that BCL2 expression is regulated by DNA methylation, associated with epithelial-mesenchymal transition, and increased by the neuronal transcription factor ASCL1. Finally, BCL2 inhibition had antitumor activity in some, but not all, BCL2-positive PC models, highlighting the need for combination strategies to enhance tumor cell apoptosis and enrich response.", "doi": "10.1172/JCI179998", "pmid": "39286979", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC11405043"}, {"db": "pii", "key": "179998"}], "notes": [], "created": "2025-11-14T07:49:55.957Z", "modified": "2026-01-03T12:42:01.813Z"}, {"entity": "publication", "iuid": "2749014de2334181bacad583b927535e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2749014de2334181bacad583b927535e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2749014de2334181bacad583b927535e"}}, "title": "An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression.", "authors": [{"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Chesner", "given": "Lisa N", "initials": "LN", "orcid": "0009-0007-2779-8824", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ee8b85578474244893baffac823a58c.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Zhou", "given": "Stanley", "initials": "S", "orcid": "0000-0001-8187-0128", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e22a4caa4fe04b2bbf6af8d5149f0383.json"}}, {"family": "Foye", "given": "Adam", "initials": "A", "orcid": "0000-0002-9910-9836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74c8c402b4a243ab95b9d20ecc43d4b9.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Weinstein", "given": "Alana S", "initials": "AS", "orcid": "0000-0002-1563-9072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e16ba4d459704a96adc34a85197bab05.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Zhu", "given": "Xiaolin", "initials": "X", "orcid": "0000-0002-3221-595X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9.json"}}, {"family": "Moreno-Rodriguez", "given": "Thaidy", "initials": "T", "orcid": "0000-0003-3588-3889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be9adfae1d354f85a76d66de8bc08cba.json"}}, {"family": "Li", "given": "Haolong", "initials": "H", "orcid": "0000-0002-8628-9698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbc2d2abba854008b56d417e6083614c.json"}}, {"family": "SU2C/PCF West Coast Prostate Cancer Dream Team", "given": "", "initials": ""}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}}, {"family": "Lupien", "given": "Mathieu", "initials": "M", "orcid": "0000-0003-0929-9478", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1967a3e4d1ff43998c93ea10d874cd01.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}], "type": "journal article", "published": "2024-09-16", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "84", "issue": "18", "pages": "3086-3100", "issn-l": "0008-5472"}, "abstract": "Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights into the drivers of therapy resistance. In this study, we produced chromatin accessibility maps linked to the binding of lineage-specific transcription factors (TF) by performing assay for transposase-accessible chromatin sequencing on 70 mCRPC tissue biopsies integrated with transcriptome and whole-genome sequencing. mCRPC had a distinct global chromatin accessibility profile linked to AR function. Analysis of TF occupancy across accessible chromatin revealed 203 TFs associated with mCRPC subtypes. Notably, ZNF263 was identified as a putative prostate cancer TF with a significant impact on gene activity in the double-negative subtype (AR- neuroendocrine-), potentially activating MYC targets. Overall, this analysis of chromatin accessibility in mCRPC provides valuable insights into epigenetic changes that occur during progression to mCRPC. Significance: Integration of a large cohort of transcriptome, whole-genome, and ATAC sequencing characterizes the chromatin accessibility changes in advanced prostate cancer and identifies therapy-resistant prostate cancer subtype-specific transcription factors that modulate oncogenic programs.", "doi": "10.1158/0008-5472.CAN-24-0890", "pmid": "38990734", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS2049608"}, {"db": "pmc", "key": "PMC12248187"}, {"db": "pii", "key": "746391"}], "notes": [], "created": "2025-11-14T07:49:57.398Z", "modified": "2025-11-14T07:49:57.837Z"}, {"entity": "publication", "iuid": "66ba9aefeb424a47927a105ce3d9e02a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/66ba9aefeb424a47927a105ce3d9e02a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/66ba9aefeb424a47927a105ce3d9e02a"}}, "title": "Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer.", "authors": [{"family": "Zhu", "given": "Xiaolin", "initials": "X"}, {"family": "Farsh", "given": "Tatyanah", "initials": "T"}, {"family": "Vis", "given": "Dani\u00ebl", "initials": "D"}, {"family": "Yu", "given": "Ivan", "initials": "I"}, {"family": "Li", "given": "Haolong", "initials": "H"}, {"family": "Liu", "given": "Tianyi", "initials": "T"}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M"}, {"family": "Shrestha", "given": "Raunak", "initials": "R"}, {"family": "Kneppers", "given": "Jeroen", "initials": "J"}, {"family": "Severson", "given": "Tesa", "initials": "T"}, {"family": "Zhang", "given": "Meng", "initials": "M"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Moreno Rodriguez", "given": "Thaidy", "initials": "T"}, {"family": "Weinstein", "given": "Alana S", "initials": "AS"}, {"family": "Foye", "given": "Adam", "initials": "A"}, {"family": "Mehra", "given": "Niven", "initials": "N"}, {"family": "Aggarwal", "given": "Rahul R", "initials": "RR"}, {"family": "Bergman", "given": "Andries M", "initials": "AM"}, {"family": "Small", "given": "Eric J", "initials": "EJ"}, {"family": "Lack", "given": "Nathan A", "initials": "NA"}, {"family": "Zwart", "given": "Wilbert", "initials": "W"}, {"family": "Quigley", "given": "David A", "initials": "DA"}, {"family": "van der Heijden", "given": "Michiel S", "initials": "MS"}, {"family": "Feng", "given": "Felix Y", "initials": "FY"}], "type": "journal article", "published": "2024-08-13", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "134", "issue": "19", "issn-l": "0021-9738"}, "abstract": "BACKGROUNDAndrogen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance.METHODSTo investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line.RESULTSWe confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.", "doi": "10.1172/JCI178604", "pmid": "39352383", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC11444163"}, {"db": "pii", "key": "178604"}], "notes": [], "created": "2025-11-14T07:50:00.511Z", "modified": "2026-01-03T12:42:33.115Z"}, {"entity": "publication", "iuid": "468d8c3dab1c48d889d35d3e63b16ac1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/468d8c3dab1c48d889d35d3e63b16ac1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/468d8c3dab1c48d889d35d3e63b16ac1"}}, "title": "Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer.", "authors": [{"family": "Zhao", "given": "Shuang G", "initials": "SG", "orcid": "0000-0002-9166-6507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7d9e7e456be4376adb63a3e5ab895a7.json"}}, {"family": "Bootsma", "given": "Matthew", "initials": "M"}, {"family": "Zhou", "given": "Stanley", "initials": "S", "orcid": "0000-0001-8187-0128", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e22a4caa4fe04b2bbf6af8d5149f0383.json"}}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Moreno-Rodriguez", "given": "Thaidy", "initials": "T", "orcid": "0000-0003-3588-3889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be9adfae1d354f85a76d66de8bc08cba.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Pan", "given": "Chu", "initials": "C"}, {"family": "Arlidge", "given": "Christopher", "initials": "C"}, {"family": "Hawley", "given": "James R", "initials": "JR"}, {"family": "Foye", "given": "Adam", "initials": "A"}, {"family": "Weinstein", "given": "Alana S", "initials": "AS", "orcid": "0000-0002-1563-9072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e16ba4d459704a96adc34a85197bab05.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Li", "given": "Haolong", "initials": "H", "orcid": "0000-0002-8628-9698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbc2d2abba854008b56d417e6083614c.json"}}, {"family": "Chesner", "given": "Lisa N", "initials": "LN"}, {"family": "Rydzewski", "given": "Nicholas R", "initials": "NR"}, {"family": "Helzer", "given": "Kyle T", "initials": "KT", "orcid": "0000-0003-3853-5564", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7011e2b72c254794baf945f716d3372d.json"}}, {"family": "Shi", "given": "Yue", "initials": "Y", "orcid": "0000-0002-2860-2666", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6128013110c14fedaef6e2ad9924006c.json"}}, {"family": "West Coast Dream Team Consortium", "given": "", "initials": ""}, {"family": "Lynch", "given": "Molly", "initials": "M"}, {"family": "Dehm", "given": "Scott M", "initials": "SM", "orcid": "0000-0002-7827-5579", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb947d721b424bb190ddf41a808a2cb0.json"}}, {"family": "Lang", "given": "Joshua M", "initials": "JM", "orcid": "0000-0002-0943-8872", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d37a2599fa044894abc8642baa80e00b.json"}}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "He", "given": "Hansen H", "initials": "HH", "orcid": "0000-0003-2898-3363", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/487cb044249647b2a1608be1a33dff98.json"}}, {"family": "Wyatt", "given": "Alexander W", "initials": "AW", "orcid": "0000-0003-2399-0329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41e8ef800a344c68be341f0691438260.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Zwart", "given": "Wilbert", "initials": "W", "orcid": "0000-0002-9823-7289", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/014603af06df4629b83fb3e7aa17710a.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}, {"family": "Lupien", "given": "Mathieu", "initials": "M"}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "volume": "56", "issue": "8", "pages": "1689-1700", "issn-l": "1061-4036"}, "abstract": "The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2-ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.", "doi": "10.1038/s41588-024-01826-3", "pmid": "39020220", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC11319208"}, {"db": "pii", "key": "10.1038/s41588-024-01826-3"}], "notes": [], "created": "2025-11-14T07:50:01.698Z", "modified": "2025-11-14T07:50:01.999Z"}, {"entity": "publication", "iuid": "b9950ef7523f4c7880d948806d4a7f0d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b9950ef7523f4c7880d948806d4a7f0d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b9950ef7523f4c7880d948806d4a7f0d"}}, "title": "Integrative analysis of ultra-deep RNA-seq reveals alternative promoter usage as a mechanism of activating oncogenic programmes during prostate cancer progression.", "authors": [{"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Cui", "given": "Xiekui", "initials": "X"}, {"family": "Foye", "given": "Adam", "initials": "A"}, {"family": "Farh", "given": "Kyle", "initials": "K"}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Dang", "given": "Ha X", "initials": "HX", "orcid": "0000-0002-9342-9249", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0a111bbe28044d3c93a4476769bcfb6c.json"}}, {"family": "Li", "given": "Haolong", "initials": "H"}, {"family": "Febbo", "given": "Phillip G", "initials": "PG", "orcid": "0000-0002-6496-4664", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb238880a5de47579326ae0d8008119d.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R"}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ"}, {"family": "SU2C/PCF West Coast Prostate Cancer Dream Team", "given": "", "initials": ""}, {"family": "Maher", "given": "Christopher A", "initials": "CA", "orcid": "0000-0002-9035-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d6e57151d8f42b3af517e57cd09baa0.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}], "type": "journal article", "published": "2024-07-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "26", "issue": "7", "pages": "1176-1186", "issn-l": "1465-7392"}, "abstract": "Transcription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood. Here we show, using deep RNA sequencing in 274 biopsies of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer, that AP usage increases as tumours progress and APs are responsible for a disproportionate amount of tumour transcriptional activity. Expression of the androgen receptor (AR), the key driver of prostate tumour activity, is correlated with elevated AP usage. We identified AR, FOXA1 and MYC as potential drivers of AP activation. DNA methylation is a likely mechanism for AP activation during tumour progression and lineage plasticity. Our data suggest that prostate tumours activate APs to magnify the transcriptional impact of tumour drivers, including AR and MYC.", "doi": "10.1038/s41556-024-01438-3", "pmid": "38871824", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS2049615"}, {"db": "pmc", "key": "PMC11844022"}, {"db": "pii", "key": "10.1038/s41556-024-01438-3"}], "notes": [], "created": "2025-11-14T07:50:03.288Z", "modified": "2025-11-14T07:50:03.458Z"}, {"entity": "publication", "iuid": "566d0bcd091c4efb9a0c8621c74affb7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/566d0bcd091c4efb9a0c8621c74affb7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/566d0bcd091c4efb9a0c8621c74affb7"}}, "title": "The Genomic and Epigenomic Landscape of Double-Negative Metastatic Prostate Cancer.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Li", "given": "Haolong", "initials": "H", "orcid": "0000-0002-8628-9698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbc2d2abba854008b56d417e6083614c.json"}}, {"family": "Zhang", "given": "Li", "initials": "L", "orcid": "0000-0002-3617-2627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a197e422e644bd38f0d69f33e653ac7.json"}}, {"family": "Foye", "given": "Adam", "initials": "A", "orcid": "0000-0002-9910-9836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74c8c402b4a243ab95b9d20ecc43d4b9.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Chou", "given": "Jonathan", "initials": "J", "orcid": "0000-0003-1258-0391", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4a72f7d3b2d4f72a8ebfc23f36f3714.json"}}, {"family": "Chang", "given": "Kevin", "initials": "K", "orcid": "0000-0001-6227-6430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/703469ab773341ae86aa8c0a44968b2f.json"}}, {"family": "Moreno-Rodriguez", "given": "Thaidy", "initials": "T", "orcid": "0000-0003-3588-3889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be9adfae1d354f85a76d66de8bc08cba.json"}}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Baskin", "given": "Avi", "initials": "A", "orcid": "0000-0002-1016-2025", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d74a04ff676b4051b905f344e90a00ac.json"}}, {"family": "Zhu", "given": "Xiaolin", "initials": "X", "orcid": "0000-0002-3221-595X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9.json"}}, {"family": "Weinstein", "given": "Alana S", "initials": "AS", "orcid": "0000-0002-1563-9072", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e16ba4d459704a96adc34a85197bab05.json"}}, {"family": "Younger", "given": "Noah", "initials": "N", "orcid": "0000-0001-5536-6999", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ef8306568e64bd0935d6ecaad78cf89.json"}}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "Beer", "given": "Tomasz M", "initials": "TM", "orcid": "0000-0001-5600-9993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c828b8adf0944e72aaacab129733f181.json"}}, {"family": "Chi", "given": "Kim N", "initials": "KN", "orcid": "0000-0002-3782-7226", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ee7573962f6411688894c17260e1095.json"}}, {"family": "Evans", "given": "Christopher P", "initials": "CP", "orcid": "0000-0001-5626-8901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8a9ee6f18f94c9ea82f34401edc3467.json"}}, {"family": "Gleave", "given": "Martin", "initials": "M", "orcid": "0000-0003-4235-0167", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f3a7aa50e3874927b1db062aa35b415d.json"}}, {"family": "Lara", "given": "Primo N", "initials": "PN", "orcid": "0000-0001-9512-0002", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9baabb4a6be4dfd9dad6ab7bcb8319d.json"}}, {"family": "Reiter", "given": "Rob E", "initials": "RE", "orcid": "0000-0002-7962-3985", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a81ac4aa295d40d6825364129548f95d.json"}}, {"family": "Rettig", "given": "Matthew B", "initials": "MB", "orcid": "0000-0002-7394-3056", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/df1dd288962643beb53cce332f615144.json"}}, {"family": "Witte", "given": "Owen N", "initials": "ON", "orcid": "0000-0003-4461-4533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435dcbfb32af474a9027576c7dc49ec6.json"}}, {"family": "Wyatt", "given": "Alexander W", "initials": "AW", "orcid": "0000-0003-2399-0329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41e8ef800a344c68be341f0691438260.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}], "type": "journal article", "published": "2023-08-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "83", "issue": "16", "pages": "2763-2774", "issn-l": "0008-5472"}, "abstract": "Systemic targeted therapy in prostate cancer is primarily focused on ablating androgen signaling. Androgen deprivation therapy and second-generation androgen receptor (AR)-targeted therapy selectively favor the development of treatment-resistant subtypes of metastatic castration-resistant prostate cancer (mCRPC), defined by AR and neuroendocrine (NE) markers. Molecular drivers of double-negative (AR-/NE-) mCRPC are poorly defined. In this study, we comprehensively characterized treatment-emergent mCRPC by integrating matched RNA sequencing, whole-genome sequencing, and whole-genome bisulfite sequencing from 210 tumors. AR-/NE- tumors were clinically and molecularly distinct from other mCRPC subtypes, with the shortest survival, amplification of the chromatin remodeler CHD7, and PTEN loss. Methylation changes in CHD7 candidate enhancers were linked to elevated CHD7 expression in AR-/NE+ tumors. Genome-wide methylation analysis nominated Kr\u00fcppel-like factor 5 (KLF5) as a driver of the AR-/NE- phenotype, and KLF5 activity was linked to RB1 loss. These observations reveal the aggressiveness of AR-/NE- mCRPC and could facilitate the identification of therapeutic targets in this highly aggressive disease.\n\nComprehensive characterization of the five subtypes of metastatic castration-resistant prostate cancer identified transcription factors that drive each subtype and showed that the double-negative subtype has the worst prognosis.", "doi": "10.1158/0008-5472.CAN-23-0593", "pmid": "37289025", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC10425725"}, {"db": "pii", "key": "727214"}], "notes": [], "created": "2025-11-14T07:50:04.624Z", "modified": "2025-11-14T07:50:05.101Z"}, {"entity": "publication", "iuid": "f6fa8d20bb97447395117dfa447db2c5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f6fa8d20bb97447395117dfa447db2c5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f6fa8d20bb97447395117dfa447db2c5"}}, "title": "Intrinsic Molecular Subtypes of Metastatic Castration-Resistant Prostate Cancer.", "authors": [{"family": "Feng", "given": "Eric", "initials": "E", "orcid": "0000-0002-0906-0558", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc1adaa53615451bbe7b019a16bcd5ff.json"}}, {"family": "Rydzewski", "given": "Nicholas R", "initials": "NR", "orcid": "0000-0002-9465-9441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2274f0d17a124161ae74c957a1cfef07.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Bootsma", "given": "Matthew", "initials": "M", "orcid": "0000-0003-0879-5066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e05e082928c444a6b7750cf5476f3953.json"}}, {"family": "Helzer", "given": "Kyle T", "initials": "KT", "orcid": "0000-0003-3853-5564", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7011e2b72c254794baf945f716d3372d.json"}}, {"family": "Lang", "given": "Joshua M", "initials": "JM", "orcid": "0000-0002-0943-8872", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d37a2599fa044894abc8642baa80e00b.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Zhao", "given": "Shuang G", "initials": "SG", "orcid": "0000-0002-9166-6507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7d9e7e456be4376adb63a3e5ab895a7.json"}}], "type": "journal article", "published": "2022-12-15", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "volume": "28", "issue": "24", "pages": "5396-5404", "issn-l": "1078-0432"}, "abstract": "Although numerous biology-driven subtypes have been described previously in metastatic castration-resistant prostate cancer (mCRPC), unsupervised molecular subtyping based on gene expression has been less studied, especially using large cohorts. Thus, we sought to identify the intrinsic molecular subtypes of mCRPC and assess molecular and clinical correlates in the largest combined cohort of mCRPC samples with gene expression data available to date.\n\nWe combined and batch-effect corrected gene expression data from four mCRPC cohorts from the Fred Hutchinson Cancer Research Center (N = 157), a small-cell neuroendocrine (NE) prostate cancer (SCNC)-enriched cohort from Weill Cornell Medicine (N = 49), and cohorts from the Stand Up 2 Cancer/Prostate Cancer Foundation East Coast Dream Team (N = 266) and the West Coast Dream Team (N = 162).\n\nHierarchical clustering of RNA-sequencing data from these 634 mCRPC samples identified two distinct adenocarcinoma subtypes, one of which (adeno-immune) was characterized by higher gene expression of immune pathways, higher CIBERSORTx immune scores, diminished ASI benefit, and non-lymph node metastasis tropism compared with an adeno-classic subtype. We also identified two distinct subtypes with enrichment for an NE phenotype, including an NE-liver subgroup characterized by liver metastasis tropism, PTEN loss, and APC and SPOP mutations compared with an NE-classic subgroup.\n\nOur results emphasize the heterogeneity of mCRPC beyond currently accepted molecular phenotypes, and suggest that future studies should consider incorporating transcriptome-wide profiling to better understand how these differences impact treatment responses and outcomes.", "doi": "10.1158/1078-0432.CCR-22-2567", "pmid": "36260524", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS1845221"}, {"db": "pmc", "key": "PMC9890931"}, {"db": "pii", "key": "709863"}], "notes": [], "created": "2025-11-14T07:50:06.218Z", "modified": "2025-11-14T07:51:43.990Z"}, {"entity": "publication", "iuid": "995c9d0360cd4a8697f31e6faee4eef6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/995c9d0360cd4a8697f31e6faee4eef6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/995c9d0360cd4a8697f31e6faee4eef6"}}, "title": "The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.", "authors": [{"family": "Sj\u00f6str\u00f6m", "given": "Martin", "initials": "M", "orcid": "0000-0002-2629-9966", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b42d7aeedc844018bbe28980b73cb6c6.json"}}, {"family": "Zhao", "given": "Shuang G", "initials": "SG"}, {"family": "Levy", "given": "Samuel", "initials": "S", "orcid": "0000-0002-4444-5103", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d205805d1cfb4e71ace25822afb039cb.json"}}, {"family": "Zhang", "given": "Meng", "initials": "M", "orcid": "0000-0003-1042-6294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d24c6c51c024ac0b27a5162c4c2fa91.json"}}, {"family": "Ning", "given": "Yuhong", "initials": "Y"}, {"family": "Shrestha", "given": "Raunak", "initials": "R", "orcid": "0000-0002-1144-1413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ee8056667cd46ecbec79e2789ae8029.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Herberts", "given": "Cameron", "initials": "C", "orcid": "0000-0002-9929-8374", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/951e9991fa8a46708c499649d1b6da59.json"}}, {"family": "Foye", "given": "Adam", "initials": "A", "orcid": "0000-0002-9910-9836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74c8c402b4a243ab95b9d20ecc43d4b9.json"}}, {"family": "Aggarwal", "given": "Rahul", "initials": "R", "orcid": "0000-0001-7003-7982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc6eb510bedd42bbb6f57e03e724efba.json"}}, {"family": "Hua", "given": "Junjie T", "initials": "JT", "orcid": "0000-0002-1197-1174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac6c246ec5104f86a2eae545eb2a8155.json"}}, {"family": "Li", "given": "Haolong", "initials": "H"}, {"family": "Bergamaschi", "given": "Anna", "initials": "A", "orcid": "0000-0001-8709-1766", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e4bf75e08ef47cda746d7ef8d563b78.json"}}, {"family": "Maurice-Dror", "given": "Corinne", "initials": "C", "orcid": "0000-0003-4455-4497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e527b177e77f42188e783b702851d298.json"}}, {"family": "Maheshwari", "given": "Ashutosh", "initials": "A"}, {"family": "Chen", "given": "Sujun", "initials": "S"}, {"family": "Ng", "given": "Sarah W S", "initials": "SWS", "orcid": "0000-0002-7647-6940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7d889d4ea89443ef9898994e886fab85.json"}}, {"family": "Ye", "given": "Wenbin", "initials": "W", "orcid": "0000-0002-9303-9363", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b717fa60edd4b7aa6e7dc899bff0767.json"}}, {"family": "Petricca", "given": "Jessica", "initials": "J"}, {"family": "Fraser", "given": "Michael", "initials": "M"}, {"family": "Chesner", "given": "Lisa", "initials": "L"}, {"family": "Perry", "given": "Marc D", "initials": "MD", "orcid": "0000-0001-6476-2942", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/78f79ccc14c042b49c4b223887c717ed.json"}}, {"family": "Moreno-Rodriguez", "given": "Thaidy", "initials": "T", "orcid": "0000-0003-3588-3889", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be9adfae1d354f85a76d66de8bc08cba.json"}}, {"family": "Chen", "given": "William S", "initials": "WS"}, {"family": "Alumkal", "given": "Joshi J", "initials": "JJ", "orcid": "0000-0003-1278-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92169d39d28f4819959b032eff1b1b80.json"}}, {"family": "Chou", "given": "Jonathan", "initials": "J", "orcid": "0000-0003-1258-0391", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4a72f7d3b2d4f72a8ebfc23f36f3714.json"}}, {"family": "Morgans", "given": "Alicia K", "initials": "AK"}, {"family": "Beer", "given": "Tomasz M", "initials": "TM", "orcid": "0000-0001-5600-9993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c828b8adf0944e72aaacab129733f181.json"}}, {"family": "Thomas", "given": "George V", "initials": "GV"}, {"family": "Gleave", "given": "Martin", "initials": "M"}, {"family": "Lloyd", "given": "Paul", "initials": "P", "orcid": "0000-0003-3508-5553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/96da8d6dbf344cf9a2e36a864ad8ab57.json"}}, {"family": "Phillips", "given": "Tierney", "initials": "T"}, {"family": "McCarthy", "given": "Erin", "initials": "E", "orcid": "0000-0002-3845-4142", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/122a0753d84d47649be4060eb51e8a4d.json"}}, {"family": "Haffner", "given": "Michael C", "initials": "MC", "orcid": "0000-0003-0809-6425", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cce395fe9a8b4fcdaec08d5d1cb37dde.json"}}, {"family": "Zoubeidi", "given": "Amina", "initials": "A", "orcid": "0000-0002-0498-142X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a96ebc9e3f464db8b25305742981ed8d.json"}}, {"family": "Annala", "given": "Matti", "initials": "M"}, {"family": "Reiter", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-7962-3985", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a81ac4aa295d40d6825364129548f95d.json"}}, {"family": "Rettig", "given": "Matthew B", "initials": "MB", "orcid": "0000-0002-7394-3056", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/df1dd288962643beb53cce332f615144.json"}}, {"family": "Witte", "given": "Owen N", "initials": "ON", "orcid": "0000-0003-4461-4533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435dcbfb32af474a9027576c7dc49ec6.json"}}, {"family": "Fong", "given": "Lawrence", "initials": "L", "orcid": "0000-0002-6428-428X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0124854879b543d8b9653fd99cce332c.json"}}, {"family": "Bose", "given": "Rohit", "initials": "R", "orcid": "0000-0002-6785-0697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af6c55d3791a4419813918497eef18b3.json"}}, {"family": "Huang", "given": "Franklin W", "initials": "FW"}, {"family": "Luo", "given": "Jianhua", "initials": "J", "orcid": "0000-0002-0943-8872", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d37a2599fa044894abc8642baa80e00b.json"}}, {"family": "Bjartell", "given": "Anders", "initials": "A"}, {"family": "Lang", "given": "Joshua M", "initials": "JM", "orcid": "0000-0002-0943-8872", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d37a2599fa044894abc8642baa80e00b.json"}}, {"family": "Mahajan", "given": "Nupam P", "initials": "NP", "orcid": "0000-0002-4150-602X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7e3a532024d413585c0b943b37de3e5.json"}}, {"family": "Lara", "given": "Primo N", "initials": "PN"}, {"family": "Evans", "given": "Christopher P", "initials": "CP", "orcid": "0000-0001-5626-8901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8a9ee6f18f94c9ea82f34401edc3467.json"}}, {"family": "Tran", "given": "Phuoc T", "initials": "PT", "orcid": "0000-0002-0147-0376", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa2bdba7d34d48b89dd173cd0af631f1.json"}}, {"family": "Posadas", "given": "Edwin M", "initials": "EM", "orcid": "0000-0001-8649-1346", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50ac1885a27d499b863843697d82d870.json"}}, {"family": "He", "given": "Chuan", "initials": "C"}, {"family": "Cui", "given": "Xiao-Long", "initials": "XL"}, {"family": "Huang", "given": "Jiaoti", "initials": "J"}, {"family": "Zwart", "given": "Wilbert", "initials": "W", "orcid": "0000-0002-9823-7289", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/014603af06df4629b83fb3e7aa17710a.json"}}, {"family": "Gilbert", "given": "Luke A", "initials": "LA"}, {"family": "Maher", "given": "Christopher A", "initials": "CA", "orcid": "0000-0002-9035-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d6e57151d8f42b3af517e57cd09baa0.json"}}, {"family": "Boutros", "given": "Paul C", "initials": "PC", "orcid": "0000-0003-0553-7520", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8dbb2a0bed664b03b96b34bd73d65993.json"}}, {"family": "Chi", "given": "Kim N", "initials": "KN", "orcid": "0000-0002-3782-7226", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ee7573962f6411688894c17260e1095.json"}}, {"family": "Ashworth", "given": "Alan", "initials": "A", "orcid": "0000-0003-1446-7878", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/217e8097b1a14deba9247b30c1b978a7.json"}}, {"family": "Small", "given": "Eric J", "initials": "EJ"}, {"family": "He", "given": "Housheng H", "initials": "HH", "orcid": "0000-0003-2898-3363", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/487cb044249647b2a1608be1a33dff98.json"}}, {"family": "Wyatt", "given": "Alexander W", "initials": "AW", "orcid": "0000-0003-2399-0329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41e8ef800a344c68be341f0691438260.json"}}, {"family": "Quigley", "given": "David A", "initials": "DA", "orcid": "0000-0002-4726-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7672a24a905407c8b5f9d1e28deea02.json"}}, {"family": "Feng", "given": "Felix Y", "initials": "FY", "orcid": "0000-0002-0963-7687", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5af5c0e774941ac97890f17640a339e.json"}}], "type": "journal article", "published": "2022-11-02", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "82", "issue": "21", "pages": "3888-3902", "issn-l": "0008-5472"}, "abstract": "Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease.\n\nIn prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.", "doi": "10.1158/0008-5472.CAN-22-1123", "pmid": "36251389", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC9627125"}, {"db": "pii", "key": "709960"}], "notes": [], "created": "2025-11-14T07:51:45.135Z", "modified": "2025-11-14T07:51:46.107Z"}, {"entity": "publication", "iuid": "8143db0e550e4134b2ef07c0a4e06d6a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8143db0e550e4134b2ef07c0a4e06d6a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8143db0e550e4134b2ef07c0a4e06d6a"}}, "title": "Reclassifying tumour cell cycle activity in terms of its tissue of origin.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Yi", "given": "Joan Jong Jing", "initials": "JJJ", "orcid": "0000-0002-4735-301X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e2eda77a9e04bef8400ddb96fdba325.json"}}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP", "orcid": "0000-0003-2343-9772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9aa223903694c8399b89adc231facce.json"}}], "type": "journal article", "published": "2022-08-20", "journal": {"title": "NPJ Precis Oncol", "issn": "2397-768X", "volume": "6", "issue": "1", "pages": "59", "issn-l": null}, "abstract": "Genomic alterations resulting in loss of control over the cell cycle is a fundamental hallmark of human malignancies. Whilst pan-cancer studies have broadly assessed tumour genomics and their impact on oncogenic pathways, analyses taking the baseline signalling levels in normal tissue into account are lacking. To this end, we aimed to reclassify the cell cycle activity of tumours in terms of their tissue of origin and determine if any common DNA mutations, chromosome arm-level changes or signalling pathways contribute to an increase in baseline corrected cell cycle activity. Combining normal tissue and pan-cancer data from over 13,000 samples we demonstrate that tumours of gynaecological origin show the highest levels of corrected cell cycle activity, partially owing to hormonal signalling and gene expression changes. We also show that normal and tumour tissues can be separated into groups (quadrants) of low/high cell cycle activity and propose the hypothesis of an upper limit on these activity levels in tumours.", "doi": "10.1038/s41698-022-00302-7", "pmid": "35987928", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC9392789"}, {"db": "pii", "key": "10.1038/s41698-022-00302-7"}], "notes": [], "created": "2025-11-14T07:51:47.320Z", "modified": "2026-01-03T12:21:55.200Z"}, {"entity": "publication", "iuid": "e69abfcba55147bc9c0e884a88a1b87c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e69abfcba55147bc9c0e884a88a1b87c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e69abfcba55147bc9c0e884a88a1b87c"}}, "title": "B cell-related gene signature and cancer immunotherapy response.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Li", "given": "Bailiang", "initials": "B"}, {"family": "Li", "given": "Ruijiang", "initials": "R", "orcid": "0000-0002-0232-5998", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/adee5b06fdf743139a8bb3ac8bff4d4a.json"}}], "type": "journal article", "published": "2022-04-00", "journal": {"title": "Br. J. Cancer", "issn": "1532-1827", "volume": "126", "issue": "6", "pages": "899-906", "issn-l": "0007-0920"}, "abstract": "B lymphocytes have multifaceted functions in the tumour microenvironment, and their prognostic role in human cancers is controversial. Here we aimed to identify tumour microenvironmental factors that influence the prognostic effects of B cells.\n\nWe conducted a gene expression analysis of 3585 patients for whom the clinical outcome information was available. We further investigated the clinical relevance for predicting immunotherapy response.\n\nWe identified a novel B cell-related gene (BCR) signature consisting of nine cytokine signalling genes whose high expression could diminish the beneficial impact of B cells on patient prognosis. In triple-negative breast cancer, higher B cell abundance was associated with favourable survival only when the BCR signature was low (HR = 0.68, p = 0.0046). By contrast, B cell abundance had no impact on prognosis when the BCR signature was high (HR = 0.93, p = 0.80). This pattern was consistently observed across multiple cancer types including lung, colorectal, and melanoma. Further, the BCR signature predicted response to immune checkpoint blockade in metastatic melanoma and compared favourably with the established markers.\n\nThe prognostic impact of tumour-infiltrating B cells depends on the status of cytokine signalling genes, which together could predict response to cancer immunotherapy.", "doi": "10.1038/s41416-021-01674-6", "pmid": "34921229", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC8927337"}, {"db": "pii", "key": "10.1038/s41416-021-01674-6"}], "notes": [], "created": "2025-11-14T07:51:48.669Z", "modified": "2025-11-14T07:51:48.750Z"}, {"entity": "publication", "iuid": "ebb8671ddf934fd48ec54e4d95bfc70f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ebb8671ddf934fd48ec54e4d95bfc70f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ebb8671ddf934fd48ec54e4d95bfc70f"}}, "title": "Reclassifying Cancer: Defining tumour cell cycle activity in terms of its tissue of origin in over 13,000 samples", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Yi", "given": "Joan Jong Jing", "initials": "JJJ"}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS", "orcid": "0000-0002-7722-7532", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99821dac16e64ad48325a1314398b927.json"}}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}], "type": "posted-content", "published": "2022-02-18", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.02.15.480623", "pmid": null, "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [], "notes": [], "created": "2026-04-27T19:29:56.492Z", "modified": "2026-04-27T19:29:56.529Z"}, {"entity": "publication", "iuid": "c15d49242f7b4a60a9d76b23e514d949", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c15d49242f7b4a60a9d76b23e514d949.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c15d49242f7b4a60a9d76b23e514d949"}}, "title": "A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS", "orcid": "0000-0002-7722-7532", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99821dac16e64ad48325a1314398b927.json"}}, {"family": "Parker", "given": "Joel S", "initials": "JS", "orcid": "0000-0003-2080-6901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/586d6382c81c407983976de4de3c9835.json"}}, {"family": "L\u00f6verli", "given": "Elinor", "initials": "E"}, {"family": "Perou", "given": "Charles M", "initials": "CM", "orcid": "0000-0001-9827-2247", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f7179d8a91d4703ae5bdfa3e003f941.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP", "orcid": "0000-0003-2343-9772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9aa223903694c8399b89adc231facce.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "39", "issue": "32", "pages": "5430-5440", "issn-l": "0950-9232"}, "abstract": "Pan-cancer genomic analyses based on the magnitude of pathway activity are currently lacking. Focusing on the cell cycle, we examined the DNA mutations and chromosome arm-level aneuploidy within tumours with low, intermediate and high cell-cycle activity in 9515 pan-cancer patients with 32 different tumour types. Boxplots showed that cell-cycle activity varied broadly across and within all cancers. TP53 and PIK3CA mutations were common in all cell cycle score (CCS) tertiles but with increasing frequency as cell-cycle activity levels increased (P < 0.001). Mutations in BRAF and gains in 16p were less frequent in CCS High tumours (P < 0.001). In Kaplan-Meier analysis, patients whose tumours were CCS Low had a longer Progression Free Interval (PFI) relative to Intermediate or High (P < 0.001) and this significance remained in multivariable analysis (CCS Intermediate: HR = 1.37; 95% CI 1.17-1.60, CCS High: 1.54; 1.29-1.84, CCS Low = Ref). These results demonstrate that whilst similar DNA alterations can be found at all cell-cycle activity levels, some notable exceptions exist. Moreover, independent prognostic information can be derived on a pan-cancer level from a simple measure of cell-cycle activity.", "doi": "10.1038/s41388-020-1367-4", "pmid": "32581248", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS1702965"}, {"db": "pmc", "key": "PMC8159764"}, {"db": "pii", "key": "10.1038/s41388-020-1367-4"}], "notes": [], "created": "2025-11-14T07:51:50.036Z", "modified": "2026-08-09T18:52:23.385Z"}, {"entity": "publication", "iuid": "fef3a5d364cf48299a854fb7fe8081fa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fef3a5d364cf48299a854fb7fe8081fa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fef3a5d364cf48299a854fb7fe8081fa"}}, "title": "The long-term prognostic and predictive capacity of cyclin D1 gene amplification in 2305 breast tumours.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS"}, {"family": "Li", "given": "Jingmei", "initials": "J"}, {"family": "Harrell", "given": "J Chuck", "initials": "JC"}, {"family": "Darai-Ramqvist", "given": "Eva", "initials": "E"}, {"family": "Sifakis", "given": "Emmanouil G", "initials": "EG"}, {"family": "Foukakis", "given": "Theodoros", "initials": "T"}, {"family": "Perou", "given": "Charles M", "initials": "CM"}, {"family": "Czene", "given": "Kamila", "initials": "K"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP", "orcid": "0000-0003-2343-9772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9aa223903694c8399b89adc231facce.json"}}], "type": "journal article", "published": "2019-02-28", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "21", "issue": "1", "pages": "34", "issn-l": "1465-5411"}, "abstract": "Use of cyclin D1 (CCND1) gene amplification as a breast cancer biomarker has been hampered by conflicting assessments of the relationship between cyclin D1 protein levels and patient survival. Here, we aimed to clarify its prognostic and treatment predictive potential through comprehensive long-term survival analyses.\n\nCCND1 amplification was assessed using SNP arrays from two cohorts of 1965 and 340 patients with matching gene expression array and clinical follow-up data of over 15 years. Kaplan-Meier and multivariable Cox regression analyses were used to determine survival differences between CCND1 amplified vs. non-amplified tumours in clinically relevant patient sets, within PAM50 subtypes and within treatment-specific subgroups. Boxplots and differential gene expression analyses were performed to assess differences between amplified vs. non-amplified tumours within PAM50 subtypes.\n\nWhen combining both cohorts, worse survival was found for patients with CCND1-amplified tumours in luminal A (HR = 1.68; 95% CI, 1.15-2.46), luminal B (1.37; 1.01-1.86) and ER+/LN-/HER2- (1.66; 1.14-2.41) subgroups. In gene expression analysis, CCND1-amplified luminal A tumours showed increased proliferation (P < 0.001) and decreased progesterone (P = 0.002) levels along with a large overlap in differentially expressed genes when comparing luminal A and B-amplified vs. non-amplified tumours.\n\nOur results indicate that CCND1 amplification is associated with worse 15-year survival in ER+/LN-/HER2-, luminal A and luminal B patients. Moreover, luminal A CCND1-amplified tumours display gene expression changes consistent with a more aggressive phenotype. These novel findings highlight the potential of CCND1 to identify patients that could benefit from long-term treatment strategies.", "doi": "10.1186/s13058-019-1121-4", "pmid": "30819233", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "pmc", "key": "PMC6394106"}, {"db": "pii", "key": "10.1186/s13058-019-1121-4"}], "notes": [], "created": "2025-11-14T07:51:51.389Z", "modified": "2026-01-03T12:43:33.474Z"}, {"entity": "publication", "iuid": "0fece34fa5164ddb89f593377f685db3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0fece34fa5164ddb89f593377f685db3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0fece34fa5164ddb89f593377f685db3"}}, "title": "Gene Expression Signatures and Immunohistochemical Subtypes Add Prognostic Value to Each Other in Breast Cancer Cohorts.", "authors": [{"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS"}, {"family": "Harrell", "given": "J Chuck", "initials": "JC"}, {"family": "Falato", "given": "Claudette", "initials": "C"}, {"family": "Carlson", "given": "Joseph W", "initials": "JW"}, {"family": "Wright", "given": "Paul K", "initials": "PK"}, {"family": "Foukakis", "given": "Theodoros", "initials": "T"}, {"family": "Perou", "given": "Charles M", "initials": "CM"}, {"family": "Czene", "given": "Kamila", "initials": "K"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}], "type": "journal article", "published": "2017-12-15", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "volume": "23", "issue": "24", "pages": "7512-7520", "issn-l": "1078-0432"}, "abstract": "Purpose: Gene signatures and Ki67 stratify the same breast tumor into opposing good/poor prognosis groups in approximately 20% of patients. Given this discrepancy, we hypothesized that the combination of a clinically relevant signature and IHC markers may provide more prognostic information than either classifier alone.Experimental Design: We assessed Ki67 alone or combined with ER, PR and HER2 (forming IHC subtypes), and the research versions of the Genomic Grade Index, 70-gene, cell-cycle score, recurrence score (RS), and PAM50 signatures on matching TMA/whole tumor sections and microarray data in two Swedish breast cancer cohorts of 379 and 209 patients, with median follow-up of 12.4 and 12.5 years, respectively. First, we fit Cox proportional hazards models and used the change in likelihood ratio (\u0394 LR) to determine the additional prognostic information provided by signatures beyond that of (i) Ki67 and (ii) IHC subtypes. Second and uniquely, we then assessed whether signatures could compete well with pathology-based IHC classifiers by calculating the additional prognostic information of Ki67/IHC subtypes beyond signatures.Results: In cohort 1, only RS and PAM50 provided additional prognostic information beyond Ki67 and IHC subtypes (\u0394 LR-\u03c72 Ki67: RS = 12.8, PAM50 = 20.7, IHC subtypes: RS = 12.9, PAM50 = 11.7). Conversely, IHC subtypes added prognostic information beyond all signatures except PAM50. Similar results were observed in cohort 2.Conclusions: RS and PAM50 provided more prognostic information than the IHC subtypes in all breast cancer patients; however, the IHC subtypes did not add any prognostic information to PAM50. Clin Cancer Res; 23(24); 7512-20. \u00a92017 AACR.", "doi": "10.1158/1078-0432.CCR-17-1535", "pmid": "28972043", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS943047"}, {"db": "pmc", "key": "PMC5822691"}, {"db": "pii", "key": "1078-0432.CCR-17-1535"}], "notes": [], "created": "2025-11-14T07:51:52.611Z", "modified": "2026-01-03T12:25:29.300Z"}, {"entity": "publication", "iuid": "46aa415bd1c44874a382cfcf1d72822c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/46aa415bd1c44874a382cfcf1d72822c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/46aa415bd1c44874a382cfcf1d72822c"}}, "title": "PAM50 Provides Prognostic Information When Applied to the Lymph Node Metastases of Advanced Breast Cancer Patients.", "authors": [{"family": "Tobin", "given": "Nicholas P", "initials": "NP"}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS"}, {"family": "Harrell", "given": "J Chuck", "initials": "JC"}, {"family": "Foukakis", "given": "Theodoros", "initials": "T"}, {"family": "Carlsson", "given": "Lena", "initials": "L"}, {"family": "Einbeigi", "given": "Zakaria", "initials": "Z"}, {"family": "Linderholm", "given": "Barbro K", "initials": "BK"}, {"family": "Loman", "given": "Niklas", "initials": "N"}, {"family": "Malmberg", "given": "Martin", "initials": "M"}, {"family": "Fern\u00f6", "given": "M\u00e5rten", "initials": "M"}, {"family": "Czene", "given": "Kamila", "initials": "K"}, {"family": "Perou", "given": "Charles M", "initials": "CM"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Hatschek", "given": "Thomas", "initials": "T"}, {"family": "TEX Trialists Group", "given": "", "initials": ""}], "type": "journal article", "published": "2017-12-01", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "volume": "23", "issue": "23", "pages": "7225-7231", "issn-l": "1078-0432"}, "abstract": "Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting.Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan-Meier and/or multivariate Cox regression analyses.Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan-Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer-specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance.Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients. Clin Cancer Res; 23(23); 7225-31. \u00a92017 AACR.", "doi": "10.1158/1078-0432.CCR-17-2301", "pmid": "28972041", "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [{"db": "mid", "key": "NIHMS943057"}, {"db": "pmc", "key": "PMC5822712"}, {"db": "pii", "key": "1078-0432.CCR-17-2301"}], "notes": [], "created": "2025-11-14T07:51:53.765Z", "modified": "2026-01-03T12:43:49.366Z"}]}