Lack of frameshift mutations at coding mononucleotide repeats in hepatocellular carcinoma in Japanese patients

BACKGROUND. Microsatellite instability occurs frequently in hereditary nonp olyposis colorectal carcinoma, in sporadic gastrointestinal carcinoma, and in other tumors. In these tumors, slippage-related frameshift mutations hav e been detected at coding mononucleotide repeats in genes such as those for transforming grow factor-p receptor type II (TGF beta RII), mannose 6-phos phate/insulinlike growth factor II receptor (M6P/IGFIIR), hMSH3, hMSH6, and Bcl-2-associated X protein (BAX). Because these genes regulate cell growth or repair DNA mismatches, loss of their function is thought to promote tum or development. The authors screened for these frameshift mutations and inv estigated the incidence of microsatellite instability (MI) in hepatocellula r carcinoma (HCC) in Japan. METHODS. Fifty HCC samples were analyzed in this study. The authors used po lymerase chain reactions to screen for frameshift mutation at the TGF beta RII (A)(10) tract, the M6P/IGFIIR (G)(8) tract, the hMSH3 (A)(8) tract, the hMSH6 (C)(8) tract, and the BAX (G)(8) tract. For MI analysis, matched tum or and nontumor liver DNA were investigated with respect to 10 microsatelli te loci. RESULTS. No frameshift mutation was detected in any case, and only 4% of th ese cancers exhibited MI in comparisons between tumor and nontumor liver sp ecimens. CONCLUSIONS. This study suggests that frameshift mutation at coding mononuc leotide repeats within TGF beta RII, M6P/IGFIR, hMSH3, hMSH6, and BAX genes did not seem to be involved in hepatocarcinogenesis in the Japanese popula tion studied. (C) 2000 American Cancer Society.