Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

Journal Article (Journal Article)

BACKGROUND: Mutations in genes for hereditary non-polyposis colorectal cancer (HNPCC) in ovarian cancer patients remains poorly defined. We sought to estimate the frequency and characteristics of HNPCC gene mutations in a population-based sample of women with epithelial ovarian cancer. METHODS: The analysis included 1893 women with epithelial ovarian cancer ascertained from three population-based studies. Full-germline DNA sequencing of the coding regions was performed on three HNPCC genes, MLH1, MSH2 and MSH6. Collection of demographic, clinical and family history information was attempted in all women. RESULTS: Nine clearly pathogenic mutations were identified, including five in MSH6, two each in MLH1 and MSH2. In addition, 28 unique predicted pathogenic missense variants were identified in 55 patients. Pathogenic mutation carriers had an earlier mean age at diagnosis of ovarian cancer, overrepresentation of cancers with non-serous histologies and a higher number of relatives with HNPCC-related cancers. CONCLUSIONS: Our findings suggest that fewer than 1% of women with ovarian cancer harbour a germline mutation in the HNPCC genes, with overrepresentation of MSH6 mutations. This represents a lower-range estimate due to the large number of predicted pathogenic variants in which pathogenicity could not definitively be determined. Identification of mismatch repair gene mutations has the potential to impact screening and treatment decisions in these women.

Full Text

Duke Authors

Cited Authors

  • Pal, T; Akbari, MR; Sun, P; Lee, J-H; Fulp, J; Thompson, Z; Coppola, D; Nicosia, S; Sellers, TA; McLaughlin, J; Risch, HA; Rosen, B; Shaw, P; Schildkraut, J; Narod, SA

Published Date

  • November 6, 2012

Published In

Volume / Issue

  • 107 / 10

Start / End Page

  • 1783 - 1790

PubMed ID

  • 23047549

Pubmed Central ID

  • PMC3493867

Electronic International Standard Serial Number (EISSN)

  • 1532-1827

Digital Object Identifier (DOI)

  • 10.1038/bjc.2012.452


  • eng

Conference Location

  • England