title: BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer.
abstract: OBJECTIVE
  Our objective was to determine the rate of BRCA1/2 deficiency in platinum-sensitive and platinum-resistant tumors from a cohort of unselect patients with advanced epithelial ovarian cancer (EOH).
  
  
  METHODS
  BRCA1/2 mutation analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients with platinum-resistant disease. Germline DNA was analyzed in mutation carriers when normal tissue was available. BRCA expression was ascertained by quantitative rt-PCR. Associations between BRCA mutation status and expression levels and parameters of platinum response were analyzed.
  
  
  RESULTS
  Fifteen of 53 (28.3%) EOC tumors had BRCA1/2 mutations. Twelve mutations were in BRCA1, while 3 involved BRCA2. Of the 12 mutation-carriers with normal tissue available for DNA analyses, 33.3% of the mutations were found to be somatic. Three mutations were novel. The majority of BRCA mutations (73%) were identified in patients with platinum-sensitive disease. In total, 38% of platinum-sensitive tumors were found to have a BRCA mutation, compared to 17% of the platinum-resistant patients. A statistical trend toward platinum-sensitive disease was seen in BRCA mutation carriers (p=0.079). Nineteen (36%) study patients had some form of BRCA deficiency, and these patients were less likely to have platinum-resistant tumors (OR=0.29; p value=0.048).
  
  
  CONCLUSIONS
  BRCA mutations occurred more frequently in platinum-sensitive EOC than platinum-resistant disease. The high overall frequency of BRCA deficiency in EOC underscores the importance of tumor profiling as therapies targeting the DNA repair pathway are being investigated.
authors.affiliation: Magee Womens Hospital of UPMC, Pittsburgh, PA 15213, USA.
authors.forename: Rebecca Byler
authors.initials: RB
authors.lastname: Dann
authors.forename: Julie A
authors.initials: JA
authors.lastname: DeLoia
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Timms
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Zorn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Potter
authors.forename: Darl D
authors.initials: DD
authors.lastname: Flake
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Krivak
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D024682:BRCA2 Protein / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009944:Organoplatinum Compounds