Genomic Instability Study on the Japanese Familial Ovarian Cancer without Germline Mutation of BRCA1 or BRCA2 by Loss of Heterozygosity Analysis

✍ Scribed by Ikunosuke Tsuneki

• Book ID: 104455951
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 42 KB
• Volume: 28
• Category: Article
• ISSN: 1341-8076
• DOI: 10.1046/j.1341-8076.2002.00011.x

✦ Synopsis

Objective and Methods: In order to explore whether novel genes have been contributing to carcinogenesis of familial ovarian cancer in which no germline mutation of BRCA1 nor BRCA2 is found in the form of a tumor suppressor gene, we have attempted to perform loss of heterozygosity (LOH) analysis with 160 microsatellite markers. The average intermarker distance was approximately 20cM.

Results: We ascertained and performed direct sequencing of available in all 63 families for mutational analysis in BRCA1 and BRCA2. Among 63 families, no germline mutation of BRCA1 or BRCA2 gene was detected in 40 affected patients in 19 families. The mean age at diagnosis of patients with tumors with no mutation, 45.7 years, was significantly younger than in the control cases, 54.2 years (p = 0.0001). It was observed that the frequency of LOH was more than 50%, only in tumor tissues from patients with no mutation but not in those with sporadic ovarian cancer in 5 regions; 5p13‐q31, 8pter‐p12, 8q24‐qter, 13q12‐34, and 17p13‐q25.

Conclusions: These results suggest the possibility that novel susceptibility genes for familial ovarian cancer exist in one of the 4 regions.