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dc.contributor.authorGallon, J
dc.contributor.authorLoomis, E
dc.contributor.authorCurry, E
dc.contributor.authorMartin, N
dc.contributor.authorBrody, L
dc.contributor.authorGarner, I
dc.contributor.authorBrown, R
dc.contributor.authorFlanagan, JM
dc.date.accessioned2021-08-12T08:57:54Z
dc.date.available2021-08-12T08:57:54Z
dc.date.issued2021-06-05
dc.identifier.citationClinical epigenetics, 2021, 13 (1), pp. 122 - ?
dc.identifier.issn1868-7075
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4740
dc.identifier.eissn1868-7083
dc.identifier.doi10.1186/s13148-021-01105-6
dc.description.abstractBACKGROUND: Resistance to DNA damaging chemotherapies leads to cancer treatment failure and poor patient prognosis. We investigated how genomic distribution of accessible chromatin sites is altered during acquisition of cisplatin resistance using matched ovarian cell lines from high grade serous ovarian cancer (HGSOC) patients before and after becoming clinically resistant to platinum-based chemotherapy. RESULTS: Resistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Clusters of cis-regulatory elements at these intergenic regions show chromatin changes that are associated with altered expression of linked genes, with enrichment for genes involved in the Fanconi anemia/BRCA DNA damage response pathway. Further, genome-wide distribution of platinum adducts associates with the chromatin changes observed and distinguish sensitive from resistant lines. In the resistant line, we observe fewer adducts around gene promoters and more adducts at intergenic regions. CONCLUSIONS: Chromatin changes at intergenic regulators of gene expression are associated with in vivo derived drug resistance and Pt-adduct distribution in patient-derived HGSOC drug resistance models.
dc.formatElectronic
dc.format.extent122 - ?
dc.languageeng
dc.language.isoeng
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleChromatin accessibility changes at intergenic regions are associated with ovarian cancer drug resistance.
dc.typeJournal Article
dcterms.dateAccepted2021-05-17
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1186/s13148-021-01105-6
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-06-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical epigenetics
pubs.issue1
pubs.notesNot known
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
pubs.publication-statusPublished
pubs.volume13
pubs.embargo.termsNot known
icr.researchteamMedicine (Brown Epigenetic Therapy)
icr.researchteamMedicine (Brown Epigenetic Therapy)
dc.contributor.icrauthorBrown, Robert


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