A TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE MUTATION COMMON IN SPORADIC CECUM CANCER WITH MICROSATELLITE INSTABILITY

Mismatch repair genes are the responsible genes for hereditary nonpoly posis colon cancer, and mutation of these genes causes replication err or (RER).In several RER-positive colon cancer cell: lines, mutations o f repetitive sequences of transforming growth factor beta (TGF-beta) t ype II receptor (RII) gene have been reported. Since TGF-beta inhibits cell proliferation, loss of response to TGF-beta is an important tumo r progression step. In this study, the relationship between RER status and mutation of the RII gene was analyzed in 112 cases of various typ es of sporadic gastrointestinal and hepatobiliary cancer (41 with gast ric, 49 with colorectal, 5 with gallbladder, and 17 with hepatic cance rs). RER was found in 17 cases (4 with gastric, 12 with colorectal, an d 1 with gallbladder cancer), and 10 of those (3 with gastric and 7 wi th colorectal cancer) showed mutations of the RII gene. Of interest wa s that in ail seven cases with colorectal cancer, tumors were located at the cecum. These data indicate that mutation of the RII gene, presu mably caused by ahnormality of repair gene, play an important role in carcinogenesis of sporadic gastrointestinal cancer, especially at the cecum.