Mutations of the bak gene in human gastric and colorectal cancers

The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR- based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colore ctal cancers (6 early-stage and 14 advanced-stage cancers). The data herein demonstrate, for the first time, the mutation of the bak gene in gastric a nd colorectal cancers. Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence a lterations without amino acid alteration were observed 1 of 24 (4.2%) gastr ic cancers and 2 of 20 (10.0%) colorectal canters. Mutations in the bak gen e were observed only in advanced-stage gastrointestinal cancers but not in early-stage cancers. Our observations suggest that mutations in this gene p redispose bearers to the development of gastrointestinal malignancies in at least a subset of the cases.