Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

✍ Scribed by German Consortium for Hereditary Breast; Ovarian Cancer

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: French
• Weight: 200 KB
• Volume: 97
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1626

✦ Synopsis

Abstract

The main focus of this German‐wide multi‐center study was to establish a BRCA1__/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than ⅓ of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/__BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure. © 2001 Wiley‐Liss, Inc.