title: BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer.
abstract: The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.
authors.affiliation: Gynaecology Unit.
authors.forename: M
authors.initials: M
authors.lastname: Moschetta
authors.affiliation: Gynaecology Unit and Cancer Genetics Unit, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: George
authors.affiliation: Gynaecology Unit.
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.affiliation: Gynaecology Unit susana.banerjee@rmh.nhs.uk.
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D059765:Homologous Recombination / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
keywords: BRCA; methylation; ovarian cancer; somatic mutation