Mutation analysis in the BRCA2 gene in primary breast cancers

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Breast cancer presents as hereditary and sporadic forms, with hereditary cases linked to tumor suppressor genes like BRCA2.
• Germline mutations in BRCA2 are associated with increased breast cancer susceptibility.
• Recent findings highlight germline mutations in BRCA2 in breast cancer-prone families.

Purpose of the Study:

• To screen Japanese breast cancer patients for BRCA2 gene mutations.
• To identify germline and somatic mutations in the BRCA2 gene.
• To investigate the mechanism of a specific Alu element-induced BRCA2 mutation.

Main Methods:

• Screening of 100 primary breast cancer samples from Japanese patients.
• Utilizing Polymerase Chain Reaction - Single Strand Conformation Polymorphism (PCR-SSCP) for mutation detection.
• Analyzing mutation characteristics, including Alu element insertion and alternative splicing.

Main Results:

• Identified two germline BRCA2 mutations and one somatic mutation in the study cohort.
• One germline mutation involved an Alu element insertion into exon 22, leading to exon skipping.
• Evidence suggests retrotransposal insertion of an active Alu element caused this specific mutation.
• Somatic BRCA2 mutations were found to be rare in primary breast cancers, similar to BRCA1.

Conclusions:

• BRCA2 mutations, though less common than germline mutations, can occur in Japanese breast cancer patients.
• Alu element retrotransposition is a mechanism contributing to BRCA2 mutations in breast cancer.
• Somatic mutations in BRCA2 are infrequent in primary breast tumors.