Identification of a Novel Pathogenic Mutation in BRCA2 in a Spanish Breast-Ovarian Cancer Family

摘要

Germline mutations in the BRCA1/2 genes contribute to most of inherited breast and ovarian cancers. We analyzed a family fulfilling classical criteria of hereditary breast/ovarian cancer. After complete sequencing of coding regions and splice junctions of both genes, a nonpreviously reported mutation in BRCA2 was detected in the index case. Direct mutation detection was performed with their relatives, and three of them were also mutation carriers, two healthy males and a patient afflicted with borderline ovarian cancer. The c.2999delCT/ consists of a deletion of two bases in exon 11, in the limits of the ovarian cancer cluster region. This is a frameshift mutation that causes a disruption of the translational reading frame resulting in a stop codon 10 amino acids downstream in the 934 position of the BRCA2 protein, causing a truncation protein. This often causes a loss of function in the protein as critical parts of the amino acid chain are no longer created. Because of it, this mutation must be classified as pathogenic and can be regarded as the cause of the cancers in this family.