title: Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response.
abstract: Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that protects the genome from double-strand DNA damage. Recent studies revealed frequent somatic mutations of BRCA1/BRCA2 and hypermethylation of the promoter of BRCA1 in EOC, in addition to germline mutations. Comparison of DNA copy number changes in tumors with or without BRCA1/BRCA2 alterations, lead to the identification of several signatures that detect HR pathway defects, here named "HRness". These signatures predict platinum-sensitivity and survival in EOC, as it was previously shown for germline mutations of BRCA1/BRCA2. They are currently investigated in clinical trials as potential predictive biomarker for response to poly(ADP- ribose) polymerase inhibitors.
authors.affiliation: Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: De Picciotto
authors.affiliation: Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Wulfran
authors.initials: W
authors.lastname: Cacheux
authors.affiliation: Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.affiliation: Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland; Service of Genetic Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
authors.forename: Pierre O
authors.initials: PO
authors.lastname: Chappuis
authors.affiliation: Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland. Electronic address: intidhar.labidi-galy@hcuge.ch.
authors.forename: S Intidhar
authors.initials: SI
authors.lastname: Labidi-Galy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D059765:Homologous Recombination; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: Alkylating agents; BRCA mutation; BRCAness; HRness; Homologous recombination; Ovarian cancer; PARP inhibitor; Platinum