ArticleNature genetics2020
Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
Open access · greenAbstract read
In one paragraph
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 1 pooled it
22.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
192 citing papers in PubMed, 1 synthesis or guideline pooled it, 280 citations in OpenAlex.
- Novel Therapeutic Strategies for Metastatic Prostate Cancer Care.European urology · 2025Pooled it
- Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer.Cell reports. Medicine · 2025Trial
- Whole genome sequencing of 378 prostate cancer metastases reveals tissue selectivity for mismatch deficiency with potential therapeutic implications.Genome medicine · 2025Trial
- The molecular heterogeneity and clinical impact of genomic driver alterations in prostate cancer.Nature communications · 2026Article
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.Nature communications · 2026Article
- Article
- Androgen receptor drives divergent chromatin accessibility programs in benign and malignant prostate epithelial cells.Nucleic acids research · 2026Article
- A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026Article
- Increasing Cancer Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.bioRxiv : the preprint server for biology · 2026Article
- Identification of targets of clinical FOXA1 mutants involved in EMT and immune suppression in prostate cancer.Communications biology · 2026Article
- Dysregulation of the urea cycle - potential targets for treatment and diagnosis in prostate cancer.Expert reviews in molecular medicine · 2026Review
- Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.Endocrine-related cancer · 2026Review
- Review
- Squamous-state excursions activate APOBEC3A in cancer.bioRxiv : the preprint server for biology · 2026Article
- MECOM Function Is Critical for AR-Driven Treatment-Resistant Prostate Cancer.Cancer research · 2026Article
- Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer.Genome biology · 2026Article
- The pathoanatomy of cancer: order in paradox.EBioMedicine · 2026Review
- Disruption of androgen receptor-cofactor interactions by the RNA-binding protein FUS/TLS alters androgen signalling in prostate cancer.Oncogene · 2026Article
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
43 authors at 10 institutions in 2 countries.
Mark M Pomerantz *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Xintao Qiu *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8560-7017
Yanyun Zhu *Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
David Y TakedaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Wenting PanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Sylvan C BacaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alexander GusevDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7980-4620
Keegan D KorthauerDepartment of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Tesa M SeversonDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Gavin HaPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-7578-7272
Srinivas R ViswanathanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ji-Heui SeoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Holly M NguyenDepartment of Urology, University of Washington, Seattle, WA, USA.
Baohui ZhangDepartment of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Bogdan PasaniucDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Claudia GiambartolomeiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2786-1225
Sarah A AlaiwiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Connor A BellDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Edward P O'ConnorDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Matthew S ChabotDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
David R StillmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Rosina LisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alba Font-TelloDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7501-2888
Lewyn LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Paloma CejasDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Andries M BergmanDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Joyce SandersDivision of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Henk G van der PoelDepartment of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Simon A GaytherCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7937-5443
Kate LawrensonCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Marcos A S FonsecaCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jessica ReddyCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Rosario I CoronaCenter for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Gleb MartovetskyActive Motif, Inc., Carlsbad, CA, USA.
Brian EganActive Motif, Inc., Carlsbad, CA, USA.ORCID http://orcid.org/0000-0002-6354-6575
Toni ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9201-3217
Leigh EllisDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4739-5049
Isla P GarrawayDepartment of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Gwo-Shu Mary LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9244-3807
Henry W LongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
Wilbert ZwartDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands. w.zwart@nki.nl.ORCID http://orcid.org/0000-0002-9823-7289
Matthew L FreedmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. mfreedman@partners.org.ORCID http://orcid.org/0000-0002-0151-1238
Harvard University · USCedars-Sinai Medical Center · USThe Netherlands Cancer Institute · NLUniversity of California, Los Angeles · USActive Motif (United States) · USBroad Institute · USDana-Farber Cancer Institute · USUniversity of Washington · USFred Hutch Cancer Center · USOncode Institute · NL
Funding
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1MUCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6MSteroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Steven P. Balk · 2013 to 2026
$25.0MElucidation of the genetic mechanisms driving prostate tumorigenesis through integrative computational and functional approachesR01CA251555 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, PASANIUC, BOGDAN · 2021 to 2025
$3.4MElucidating prostate cancer risk mechanisms through large-scale cistrome wide association studiesR01CA262577 · NCI · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, GIMELBRANT, ALEXANDER · 2022 to 2025
$3.3MDefining the epigenetic landscape in human prostate cancerR01CA193910 · NCI · DANA-FARBER CANCER INST · PI BROWN, MYLES A, FREEDMAN, MATTHEW L · 2015 to 2019
$3.1MUtilizing genetic and functional strategies to identify causal genes and allelesR01GM107427 · NIGMS · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, JOUNG, J. KEITH · 2014 to 2017
$2.0MTranscriptional Regulation of the Androgen Receptor in Prostate CancerK08CA218530 · NCI · DANA-FARBER CANCER INST · PI TAKEDA, DAVID YOSHIO · 2017 to 2019
$531kNCI NIH HHS K08 CA218530NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA092131NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA193910NCI NIH HHS R01 CA251555NCI NIH HHS R01 CA262577NIGMS NIH HHS R01 GM107427
Abstract
Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.
Indexed as
Cell LineCell Line, TumorDisease ProgressionEpigenomicsGene Expression Regulation, NeoplasticHEK293 CellsHepatocyte Nuclear Factor 3-alphaHumansMaleProstateProstatic NeoplasmsReceptors, AndrogenRegulatory Sequences, Nucleic AcidHepatocyte Nuclear Factor 3-alphaReceptors, Androgen
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