{"entity": "researcher", "timestamp": "2026-05-12T21:50:16.731Z", "family": "Zhu", "given": "Xiaolin", "initials": "X", "orcid": "0000-0002-3221-595X", "affiliations": ["Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.", "Divsion of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/30d1c66f02ef4b5abc414a110705ccf9"}}, "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": null, "issue": null, "pages": null}, "abstract": "Background\r\nTargeted 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.\r\n\r\nResults\r\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.\r\n\r\nConclusions\r\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": null, "labels": {"DDLS Fellow": null, "Arian Lundberg": null}, "xrefs": [], "notes": [], "created": "2026-04-15T19:30:46.855Z", "modified": "2026-05-04T07:58:46.740Z"}, {"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": "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": "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"}]}