Publication:
Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential

dc.contributor.coauthorKneppers, J.
dc.contributor.coauthorSeverson, T.M.
dc.contributor.coauthorSiefert, J.C.
dc.contributor.coauthorSchol, P.
dc.contributor.coauthorJoosten, S.E.P.
dc.contributor.coauthorYu, I.P.L.
dc.contributor.coauthorHuang, C.F.
dc.contributor.coauthorMorova, T.
dc.contributor.coauthorGiambartolomei, C.
dc.contributor.coauthorSeo, J.H.
dc.contributor.coauthorBaca, S.C.
dc.contributor.coauthorCarneiro, I.
dc.contributor.coauthorEmberly, E.
dc.contributor.coauthorPasaniuc, B.
dc.contributor.coauthorJerónimo, C.
dc.contributor.coauthorHenrique, R.
dc.contributor.coauthorFreedman, M.L.
dc.contributor.coauthorWessels, L.F.A.
dc.contributor.coauthorBergman, A.M.
dc.contributor.coauthorZwart, W.
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorAltıntaş, Umut Berkay
dc.contributor.kuauthorLack, Nathan Alan
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T13:52:00Z
dc.date.issued2022
dc.description.abstractAndrogen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic and form recurrent programmatic changes that differentiate disease stages, subtypes and patient outcomes. While prior studies focused on concordance between patient subgroups, inter-tumor heterogeneity of AR enhancer selectivity remains unexplored. Here we report high levels of AR chromatin binding heterogeneity in human primary prostate tumors, that overlap with heterogeneity observed in healthy prostate epithelium. Such heterogeneity has functional consequences, as somatic mutations converge on commonly-shared AR sites in primary over metastatic tissues. In contrast, less-frequently shared AR sites associate strongly with AR-driven gene expression, while such heterogeneous AR enhancer usage also distinguishes patients’ outcome. These findings indicate that epigenetic heterogeneity in primary disease is directly informative for risk of biochemical relapse. Cumulatively, our results illustrate a high level of AR enhancer heterogeneity in primary PCa driving differential expression and clinical impact.
dc.description.fulltextYES
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue1
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipWe would like to acknowledge the NKI Genomics Core Facility for Illumina sequencing and bioinformatics support and the NKI Research High-Performance Computing (RHPC) facility for computational infrastructure. We express gratitude to all members of the Zwart and Bergman lab, and members of the NKI Oncogenomics division for helpful scientific discussion. This work was supported by the Prostate Cancer Foundation (21CHAL04), Department of Defense (W81XWH-21-1-0234, W81XWH-19-1-0565), Oncode Institute and Alpe d’HuZes/KWF Dutch Cancer Society (10084).
dc.description.versionPublisher version
dc.description.volume13
dc.identifier.doi10.1038/s41467-022-35135-2
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR04074
dc.identifier.issn2041-1723
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85143105881
dc.identifier.urihttps://hdl.handle.net/20.500.14288/3967
dc.keywordsChromatin
dc.keywordsHumans
dc.keywordsMale
dc.keywordsProstate
dc.keywordsProstatic neoplasms
dc.keywordsReceptors, androgen
dc.keywordsRegulatory sequences, nucleic acid
dc.language.isoeng
dc.publisherNature Portfolio
dc.relation.grantnoNA
dc.relation.ispartofNature Communications
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/10959
dc.subjectMedicine
dc.subjectBiochemistry
dc.titleExtensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorLack, Nathan Alan
local.contributor.kuauthorAltıntaş, Umut Berkay
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Sciences and Engineering
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