Evidence map›Paper›PMID 40593552›Full record

ArticleNature communications2025

Intraindividual epigenetic heterogeneity underlying phenotypic subtypes of advanced prostate cancer.

Kei Mizuno, Sheng-Yu Ku, Varadha Balaji Venkadakrishnan, Martin K Bakht, Michael Sigouros, Joanna Chan, Anna Trigos, Jordan H Driskill, Jyothi Manohar, Abigail King and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Kei MizunoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Sheng-Yu KuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4715-1888
Varadha Balaji VenkadakrishnanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7071-4584
Martin K BakhtDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8803-2485
Michael SigourosEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0328-8359
Joanna ChanPeter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Anna TrigosPeter MacCallum Cancer Centre, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-5915-2952
Jordan H DriskillDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-4319-3845
Jyothi ManoharEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Abigail KingEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0009-0008-5358-8414
Adam G PresserDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Min Jin KimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alok K TewariDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2617-7499
Henry W LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
David QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4726-1473
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9201-3217
Steven BalkDepartment of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4546-7371
Sarah HillDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9199-9459
Juan Miguel MosqueraEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-4666-6476
David EinsteinDepartment of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Shahneen SandhuSir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-8660-4475
Mary-Ellen TaplinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Himisha BeltranDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. himisha_beltran@dfci.harvard.edu.ORCID http://orcid.org/0000-0003-3259-2226

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate CancerP50CA272390 · NCI · DANA-FARBER CANCER INST · PI Steven P. Balk, Himisha Beltran · 2023 to 2026
$12.0M
Weill Cornell Medicine (WCM) SPORE in Prostate CancerP50CA211024 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI GUDAS, LORRAINE J · 2017 to 2021
$10.9M
Molecular mechanisms underlying lineage plasticity in prostate cancerR37CA241486 · NCI · DANA-FARBER CANCER INST · PI Himisha Beltran · 2020 to 2026
$4.1M
NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA101942NCI NIH HHS P50 CA211024NCI NIH HHS P50 CA272390NCI NIH HHS R37 CA241486U.S. Department of Defense (United States Department of Defense) HT94252310407U.S. Department of Defense (United States Department of Defense) W81XWH-17-1-0653U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50 CA272390-0U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R37CA241486-01A1
6 · The paper itself

Abstract

Castration-resistant prostate cancer is a heterogeneous disease with variable phenotypes commonly observed in later stages of the disease. These include cases that retain expression of luminal markers and those that lose hormone dependence and acquire neuroendocrine features. While there are distinct transcriptomic and epigenomic differences between castration-resistant adenocarcinoma and neuroendocrine prostate cancer, the extent of overlap and degree of diversity across tumor metastases in individual patients has not been fully characterized. Here we perform combined DNA methylation, RNA-sequencing, H3K27ac, and H3K27me3 profiling across metastatic lesions from patients with CRPC/NEPC. Integrative analyses identify DNA methylation-driven gene links based on location (H3K27ac, H3K27me3, promoters, gene bodies) pointing to mechanisms underlying dysregulation of genes involved in tumor lineage (ASCL1, AR) and therapeutic targets (PSMA, DLL3, STEAP1, B7-H3). Overall, these data highlight how integration of DNA methylation with RNA-sequencing and histone marks can inform intraindividual epigenetic heterogeneity and identify putative mechanisms driving transcriptional reprogramming in castration-resistant prostate cancer.

Indexed as

Epigenesis, GeneticGenetic HeterogeneityProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantDNA MethylationGene Expression Regulation, NeoplasticHistonesHumansMalePhenotypeHistones

Identifiers

PMID40593552
PMCPMC12219151

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.