biostudies-literatureBurdett NLVictorian Cancer AgencyVictorian Cancer Agency (VCA)Department of Health | National Health and Medical Research Council (NHMRC)Department of Health | National Health and Medical Research Council6069https://www.ebi.ac.uk/biostudies/studies/S-EPMC11258338biostudies-literatureUnknown15(1)Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presentinNature communicationsTiming of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer.PMC11258338APP1161198MCRF21004APP1189939Young BRutovitz JYoung CPurdie DValmadre SGlasgow AAlaei SWain GFerguson KStewart JDalrymple CMartin KChristie EAlsop KPavlakis NCummings MManolitsas TSadkowsky TFox SEdwards LMcCartney ANicklin JStenlake ARussell PHarnett PHenderson DPierdes JOehler MKDelahunty RStuart-Harris ROtton GLinks MSumithran EMiller JWhite JMarsden DShannon JHorwood KBowtell DDLPapadimos DLoughrey MBergh TVJobling THall CNg LFGalletta LHendley JChiew YEBurdett NLWhiteman DRischin DZeps NGreen ANattress KGard GRanieri BShirley HQuinn MMileshkin LWebb PGreen LAllen DCorrish TFriedlander MLaurie RBillson VTran HHoughton RSimpson IMellon APittman KJackman LTraficante NMcNealage JGarsed DMackenzie PBowes LMalt MMurray WMcIntosh RDodd TGrygiel JWaring PBrown BHyde SJayde VCarter JPerrin LMaidens JBilic SKirsten FChenevix-Trench GSchmidt TRome RHill JHammond ITwomey LWillis MOAustralian Ovarian Cancer Study GroupSharma RFereday SBrand ABall CCamaris CBrooks JParker AJones MBurdett NClingan PChristie ELBeith JJaworski RBuck MNeesham DObermair AHarrap KBowtell DLade SWard BRobertson RGrant PBraye SChallis DMamers PHealy THacker NBlomfield PSullivan HWyld DRogers PHung JGiles DAlexander BUnderhill CO'Callaghan NGanju VDavy MJohnson DPandey APyman JDeFazio APhillips KRobbie MNevell DSusil BHaviv IBell DGertig DMoore SByth KGlavinas LFerrier ABonaventura TBegbie SCrouch RRobertson GBell RMartyn AHealy DViduka SProietto AAu-Yeung GBaron-Hay SBeale PLeung YPandeya NBlum RAshover PCrandon ABrown SfalseTiming of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer.Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presentin2024-01-01T00:00:00Z2024 Jul2026-06-01T13:21:54.001Z2025-04-06T17:12:09.082ZS-EPMC112583383902584610.1038/s41467-024-50137-y