Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability

Frameshift mutations in genes containing mononucleotide repeats are often o bserved in cancers exhibiting a high frequency of microsatellite instabilit y (MSI-H). Several tumor types, including colorectal, gastric, and endometr ial carcinomas, display this phenotype in a significant proportion of cases . We recently showed in a large series of MSI-H colorectal tumors that appr oximately 40% of them exhibited frameshift mutations in an (A)9 tract withi n the coding region of the TCF-4 gene, a crucial member of the APC/beta-cat enin/TCF pathway. In the present study, we have examined MSI-H cancers from other primary tumor sites for mutations in this new target gene. Two of 22 (9%) MSI-H primary gastric cancers and none of 23 MSI-H endometrial primar y tumors and cell lines were found to have a 1 bp deletion in the TCF-4 rep eat. In the same series of tumors we also looked for frameshift mutations i n other coding repeats localized within the TGF beta-RII, BAX, IGFIIR, hMSH 3 and hMSH6 genes. Our results suggest that the TCF-4 gene, in a similar ma nner to some of these latter genes, is differentially altered in MSI-H tumo rs from different primary sites.