ArticleNature genetics2024
Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer.
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Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38citing papers in PubMed
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Who cites it
38 citing papers in PubMed.
- Evolution of AR and Non-AR Alterations in ctDNA of Patients with Metastatic Prostate Cancer Treated in the Phase III Alliance A031201 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Spatial chromatin architecture and accessibility co-profiling of mammalian tissues.Nature methods · 2026Article
- Origins and consequences of oncogenic 3D chromatin remodelling.Nature reviews. Cancer · 2026Review
- Structural Variation and Its Roles in Plant Genomes.Plants (Basel, Switzerland) · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- Epigenetic modulation of prostate cancer disparities in men with African ancestry.Nature reviews. Urology · 2026Review
- 3D chromatin architecture in cancer: mechanisms of dysregulation and emerging therapeutic strategies.Experimental & molecular medicine · 2026Review
- Review
- Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.Endocrine-related cancer · 2026Review
- 3D genome architecture and epigenetic regulation of lineage identity in advanced prostate cancer.Endocrinology · 2026Review
- Connecting multiway enhancer-promoter interactions to changes in gene expression in cancer.bioRxiv : the preprint server for biology · 2026Article
- Rare regulatory mutations disrupt mesenchymal molecular programs driving endocardial cushion formation in bicuspid aortic valve.Nature communications · 2026Article
- Whole-genome 3D architectural screen reveals modulators of brain DNA structure.bioRxiv : the preprint server for biology · 2026Article
- Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer.Genome biology · 2026Article
- Fast and accurate resolution of ecDNA sequence using Cycle-Extractor.bioRxiv : the preprint server for biology · 2026Article
- Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma.Scientific reports · 2026Article
- A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules.Cancer research · 2026Article
- Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.Investigational new drugs · 2026Article
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Authors and funding
31 authors.
Shuang G Zhao *Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-9166-6507
Matthew Bootsma *Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
Stanley Zhou *Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-8187-0128
Raunak ShresthaDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1144-1413
Thaidy Moreno-RodriguezDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3588-3889
Arian LundbergDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6630-2787
Chu PanPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Christopher ArlidgePrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
James R HawleyPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Alana S WeinsteinDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1563-9072
Martin SjöströmDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2629-9966
Meng ZhangDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1042-6294
Haolong LiDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8628-9698
Lisa N ChesnerDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Nicholas R RydzewskiDepartment of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
Kyle T HelzerDepartment of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0003-3853-5564
Yue ShiDepartment of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-2860-2666
West Coast Dream Team Consortium
Molly LynchMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-7827-5579
Joshua M LangCarbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-0943-8872
Joshi J AlumkalDepartment of Internal Medicine, Division of Hematology-Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1278-0166
Hansen H HePrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-2898-3363
Alexander W WyattDepartment of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-2399-0329
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7003-7982
Wilbert ZwartNetherlands Cancer Institute, Oncode Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-9823-7289
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3191-6268
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4726-1473
Mathieu LupienPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Felix Y FengDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.ORCID http://orcid.org/0000-0002-0963-7687
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MUW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6MTRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6MAR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9MMolecular regulation and expression of Trop-2 in advanced prostate cancer: Identifying optimal therapeutic nichesR01CA276269 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Scott M. Dehm, Joshua Lang · 2023 to 2026
$2.6MDYNAMIC MOLECULAR EVOLUTION OF TREATMENT RESISTANT CANCERDP2CA271832 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ZHAO, SHUANG · 2021 to 2024
$2.3MTargeting Prostate Cancer Lineage Plasticity with BET Bromodomain InhibitionR01CA251245 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALUMKAL, JOSHI JAMES · 2020 to 2024
$1.9MTargeting early events in prostate cancer lineage plasticityR01CA270539 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2023 to 2026
$1.8MDeveloping New Treatment Strategies for Neuroendocrine Prostate CancerR01CA282005 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joshi James Alumkal · 2024 to 2026
$1.6MEIF | Stand Up To Cancer (SU2C) SU2C-AACR-DT0812NCI NIH HHS DP2 CA271832NCI NIH HHS P30 CA014520NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA097186NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA251245NCI NIH HHS R01 CA270539NCI NIH HHS R01 CA276269NCI NIH HHS R01 CA282005U.S. Department of Defense (United States Department of Defense) W81XWH2010799U.S. Department of Defense (United States Department of Defense) W81XWH-21-1-0046U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1DP2CA271832-01, P30 CA014520U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01 CA251245, P50 CA097186, P50 CA186786, P50 CA186786-07S1, P30 CA046592, and W81XWH-20-1-0405
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.
Indexed as
5-MethylcytosineDNA MethylationChromatinDNAEpigenesis, GeneticEpigenomicsGene Expression Regulation, NeoplasticGenome, HumanHumansMaleNeoplasm MetastasisOncogene Proteins, FusionPrognosisProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantReceptors, Androgen5-hydroxymethylcytosine5-MethylcytosineChromatinDNAOncogene Proteins, FusionReceptors, AndrogenRNATMPRSS2-ERG fusion protein, human
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