Disruption of the DNA mismatch repair system, characterized by
microsatellite instability (MI), plays an important role in the course of human
carcinogenesis by increasing the rate of mutations of genes associated with
cancers. However, it is not clear which genes are the target genes for mutation in the course of
carcinogenesis. Microsatellites within the coding region of the
transforming growth factor beta receptor type II (RII) and
insulin-like growth factor II receptor (IGF-IIR) genes were reported to be targets for mutation during the course of
carcinogenesis in MI+
tumors. Recently, somatic mutations were found in a
poly(G)8 tract in the
BCL-2-associated X protein (BAX) gene, one of the essential players in apoptosis, in some MI+
tumors. We examined mutations of BAX in MI+
cancers of various organs and found frameshift mutations at the
poly(G)8 tract in 5 of 15 (33%)
gastric cancers, 3 of 26 (12%)
endometrial cancers, and 9 of 22 (41 %)
colorectal cancers. In contrast, no such mutations were found in
pancreatic cancer. These results suggest that mutations of BAX play an important role in the course of
carcinogenesis in the stomach, colorectum, and endometrium.