Somatic genetic events in BRCA1 and BRCA2-related ovarian cancer

Published

Journal Article (Review)

An estimated 10% of all ovarian cancer cases are thought to be the result of an autosomal dominant susceptibility factor with high penetrance. Most of these cases can be attributed to germline mutations in the BRCA1 or BRCA2 tumor suppressor genes. It was initially anticipated that somatic (non-hereditary) BRCA1 and BRCA2 mutations would be as important in the development of sporadic ovarian cancer as germline (inherited) mutations are in the development of hereditary disease. This does however not seem to be the case as far fewer than expected somatic mutations in BRCA1 or BRCA2 have been found. Apart from this molecular difference, little is still known about the additional somatic genetic events involved in hereditary ovarian cancer initiation and progression. The p53 tumor suppressor gene has been studied in relation to BRCA-associated ovarian cancer and was found to play an important, but probably not essential role. Limited analysis of HER-2/neu, K-ras, c-myc and AKT2 suggests that these genes may be less important in hereditary than in sporadic ovarian cancer. From the limited data available it appears that BRCA-related ovarian cancer may be distinct from sporadic ovarian cancer regarding both germline predisposition as well as regarding the additional somatic genetic events involved in tumor initiation and progression. However, collaborative efforts to study much larger numbers of well-characterized tumor samples and appropriate sporadic controls will be needed to confirm these findings and unravel the events involved in ovarian cancer initiation and progression. The relatively new technique of Comparative Genomic Hybridization (CGH), which allows genome wide comparison of chromosomal gains and losses may be of particular interest for such studies.

Duke Authors

Cited Authors

  • Zweemer, RP; Berchuck, A; Jacobs, IJ

Published Date

  • December 1, 1999

Published In

Volume / Issue

  • 4 / 1

Start / End Page

  • 112 - 115

International Standard Serial Number (ISSN)

  • 1219-9087

Citation Source

  • Scopus