Inherited mutations in women with ovarian carcinoma

Academic Article


  • Copyright © 2016 Amer. Med. Assoc.. All Rights Reserved. Importance: Germline Mutations in BRCA1 and BRCA2 Are Relatively Com. in Women with Ovarian, Fallopian Tube, and Peritoneal Carcinoma Causing A Greatly Increased Lifetime Risk of These Cancers, but the Frequency and Relevance of Inherited Mutations in Other Genes Is Less Well Characterized. Objective: to Determine the Frequency and Importance of Germline Mutations in Cancer-Assoc. Genes in OC. Des., Setting and Participants: A Stud. Pop. of 1915woman with OC and Available Germline DNA Were Identified from the Univ. OfWashington Gynecologic Tissue Bank and from Gynecologic Oncol. Grp. Phase III Clin. Trials 218 and 262 . Patients Were Enrolled at Diagn. and Were Not Selected for Age or Fam. Hist.. Germline DNA Was Sequenced from Women with OC Using A Targeted Capture and Multiplex Sequencing Assay. Main Outcomes and Measures: Mutation Frequencies in OCwere Compared with the Natl. Heart, Lung and Blood Inst. GO Exome Sequencing Proj. and the Exome Aggregation Consortium . Clin. Characteristics and Survival Were Assessed by Mutation Status. Results: Overall, the Median Age at Diagn. Was 60 Years in Patients Recruited from UW and 61 Years in Patients Recruited from the GOG Trials. A Higher No. of Black Women Were Recruited from the GOG Trials ; but in Patients Recruited from UW, There Was A Higher Proportion of Fallopian Tube Carcinomas ; Stage i and Ii Dis. ; and Nonserous Carcinomas . of 1915 Patients, 280 Had Mutations in BRCA1 , or BRCA2 , and 8 Had Mutations in DNA Mismatch Repair Genes. Mutations in BRIP1 , RAD51C , RAD51D , PALB2 , and BARD1 Were Significantly More Com. in Patients with OC Than in the ESP or ExAC, Present in 3.3%. Race, Histologic Subtype, and Dis. Site Were Not Predictive of Mutation Frequency. Patients with A BRCA2 Mutation from the GOG Trials Had Longer Progression-free Survival and Overall Survival Compared with Those Without Mutations. Conclusions and Relevance: of 1915 Patients with OC, 347 Carried Pathogenic Germline Mutations in Genes Assoc. with OC Risk. PALB2 and BARD1 Are Suspected OC Genes and Together with Estab. OC Genes Bring the Total No. of Genes Suspected to Cause Hered. OC to 11.
  • Published In

  • JAMA Oncology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Norquist BM; Harrell MI; Brady MF; Walsh T; Lee MK; Gulsuner S; Bernards SS; Casadei S; Yi Q; Burger RA
  • Start Page

  • 482
  • End Page

  • 490
  • Volume

  • 2
  • Issue

  • 4