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dc.contributor.authorCurry, Een_US
dc.contributor.authorZeller, Cen_US
dc.contributor.authorMasrour, Nen_US
dc.contributor.authorPatten, DKen_US
dc.contributor.authorGallon, Jen_US
dc.contributor.authorWilhelm-Benartzi, CSen_US
dc.contributor.authorGhaem-Maghami, Sen_US
dc.contributor.authorBowtell, DDen_US
dc.contributor.authorBrown, Ren_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-25T11:46:36Z
dc.date.issued2018-03-15en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29339543en_US
dc.identifier0008-5472.CAN-17-1650en_US
dc.identifier.citationCancer Res, 2018, 78 (6), pp. 1383 - 1391en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3082
dc.identifier.eissn1538-7445en_US
dc.identifier.doi10.1158/0008-5472.CAN-17-1650en_US
dc.description.abstractBivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised genes may facilitate changes in transcriptional states after exposure to anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue. Gene sets with proximal bivalent marks defined in this manner were evaluated subsequently as signatures of systematic change in DNA methylation and gene expression, comparing pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. We found that gene sets harboring bivalent chromatin domains at their promoters in tumor tissue, but not normal epithelia, overlapped with Polycomb-repressive complex target genes as well as transcriptionally silenced genes in normal ovarian and tubal stem cells. The bivalently marked genes we identified in tumors before chemotherapy displayed increased promoter CpG methylation and reduced gene expression at relapse after chemotherapy of ovarian cancer. Overall, our results support the hypothesis that preexisting histone modifications at genes in a poised chromatin state may lead to epigenetic silencing during acquired drug resistance.Significance: These results suggest epigenetic targets for intervention to prevent the emergence of cancer drug resistance. Cancer Res; 78(6); 1383-91. ©2018 AACR.en_US
dc.format.extent1383 - 1391en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectCarcinoma, Ovarian Epithelialen_US
dc.subjectChromatinen_US
dc.subjectChromatin Immunoprecipitationen_US
dc.subjectCpG Islandsen_US
dc.subjectDNA Methylationen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectFemaleen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectGene Silencingen_US
dc.subjectHistone Codeen_US
dc.subjectHistonesen_US
dc.subjectHumansen_US
dc.subjectOvarian Neoplasmsen_US
dc.subjectPromoter Regions, Geneticen_US
dc.titleGenes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-01-10en_US
rioxxterms.versionofrecord10.1158/0008-5472.CAN-17-1650en_US
rioxxterms.licenseref.startdate2018-03-15en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Resen_US
pubs.issue6en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Medicine (Brown Epigenetic Therapy)
pubs.publication-statusPublisheden_US
pubs.volume78en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (Brown Epigenetic Therapy)en_US
dc.contributor.icrauthorBrown, Roberten_US


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