{"entity": "researcher", "timestamp": "2026-05-12T21:05:34.675Z", "family": "Small", "given": "Eric J", "initials": "EJ", "orcid": "0000-0003-3191-6268", "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.", "Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California.", "Department of Urology, University of California, San Francisco, San Francisco, California."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a6d3bacede42059d6bf0f2cbfe0fec"}}, "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": "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": "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": "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"}]}