Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91650
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dc.contributor.authorPatch, A.en
dc.contributor.authorChristie, E.en
dc.contributor.authorEtemadmoghadam, D.en
dc.contributor.authorGarsed, D.en
dc.contributor.authorGeorge, J.en
dc.contributor.authorFereday, S.en
dc.contributor.authorNones, K.en
dc.contributor.authorCowin, P.en
dc.contributor.authorAlsop, K.en
dc.contributor.authorBailey, P.en
dc.contributor.authorKassahn, K.en
dc.contributor.authorNewell, F.en
dc.contributor.authorQuinn, M.en
dc.contributor.authorKazakoff, S.en
dc.contributor.authorQuek, K.en
dc.contributor.authorWilhelm-Benartzi, C.en
dc.contributor.authorCurry, E.en
dc.contributor.authorLeong, H.en
dc.contributor.authorAustralian Ovarian Cancer Study Groupen
dc.contributor.authorHamilton, A.en
dc.contributor.authoret al.en
dc.date.issued2015en
dc.identifier.citationNature, 2015; 521(7553):489-494en
dc.identifier.issn0028-0836en
dc.identifier.issn1476-4687en
dc.identifier.urihttp://hdl.handle.net/2440/91650-
dc.descriptionMartin K Oehler is a member of the Australian Ovarian Cancer Study Groupen
dc.description.abstractPatients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.en
dc.description.statementofresponsibilityAnn-Marie Patch ... Karin S Kassahn ... The Australian Ovarian Cancer Study Group ... et al.en
dc.language.isoenen
dc.publisherMacmillanen
dc.rights© 2015 Macmillian Publishers Ltd.en
dc.subjectCancer genomics; Ovarian canceren
dc.titleWhole-genome characterization of chemoresistant ovarian canceren
dc.typeJournal articleen
dc.identifier.rmid0030029656en
dc.identifier.doi10.1038/nature14410en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/631701en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/400413en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/400281en
dc.identifier.pubid187331-
pubs.library.collectionPaediatrics publicationsen
pubs.library.teamDS08en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Paediatrics publications

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