Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes or ( ). - and -associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the "BRCAness&q...

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Bibliographic Details
Published in:OncoTargets and therapy 2017-01, Vol.10, p.2539-2551
Main Authors: Hollis, Robert L, Churchman, Michael, Gourley, Charlie
Format: Article
Language:English
Subjects:
Care and treatment
Clinical outcomes
Development and progression
DNA repair
Gene mutation
Genetic aspects
Health aspects
Health risk assessment
Kinases
Mutation
Ovarian cancer
Review
Systematic review
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Summary:Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes or ( ). - and -associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the "BRCAness" phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that - and -associated OCs display distinct characteristics, most notably in long-term patient survival. Furthermore, recent data indicate that the site of mutation is important with regard to platinum and PARP inhibitor sensitivity. Here, we summarize the body of research describing the BRCAness phenotype and highlight the differential implications of different mutations with regard to clinicopathologic features, therapy sensitivity and clinical outcome in OC.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S102569