Frequent Frameshift Mutations of the TCF-4 Gene in Colorectal Cancers with Microsatellite Instability

摘要: About 15% of sporadic colorectal cancers show microsatellite instability (MSI) due to the inactivation mismatch repair genes and are termed MSI-H tumors. In these tumors, frameshift mutations in coding repeats have been found within TGFbeta-RII, BAX, IGFRII that probably involved their progression. present work, we report frequent TCF-4, another target gene for instability. TCF-4 codes a transcription factor is crucial member adenomatous polyposis coil (APC)/beta-catenin/T-cell (TCF) pathway. Fifty percent (4 8) human cell lines 39% (19 49) primary tumors were 1-bp deletion an (A)9 repeat region this gene. contrast, mutation was only 1 56 non-MSI none 16 cancer lines. These results suggest selected play role tumorigenesis. Depending on different reading frames alternatively spliced mRNA, normally several isoforms could serve as modulators transcriptional activity. The one nucleotide change transactivating properties by modifying respective proportions isoforms.