THE BAX GENE, THE PROMOTER OF APOPTOSIS, IS MUTATED IN GENETICALLY UNSTABLE CANCERS OF THE COLORECTUM, STOMACH, AND ENDOMETRIUM

Disruption of the DNA mismatch repair system, characterized by microsa tellite instability (MI), plays an important role in the course of hum an carcinogenesis by increasing the rate of mutations of genes associa ted with cancers, However, it is not clear which genes are the target genes for mutation in the course of carcinogenesis, Microsatellites wi thin the coding region of the transforming growth factor beta receptor type II (RII) and insulin-like growth factor II receptor (IGF-IIR) ge nes were reported to be targets for mutation during the course of carc inogenesis 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 MIS-tumors, We examined mu tations of BAX in MI+ cancers of various organs and found frameshift m utations at the poly(G), 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 re sults suggest that mutations of BAX play an important role in the cour se of carcinogenesis in the stomach, colorectum, and endometrium.