| High frequency microsatellite instability (MSI-H) colorectal carcinomas (CRCs) display MMR deficiency and account for about 15% of human colorectal cancers. Gene inactivation via mononucleotide tract frameshift mutations is characteristic of the pathogenesis of MSI-H colorectal carcinomas. Frameshift mutations have only been described in selected candidate genes including TGFβRII, IGFIIR, BAX and others. We developed “Kangaroo”, a program capable of highly specialized searches in nucleotide and protein sequence databases. Utilizing Kangaroo, we identified genes with coding polyadenine tracts that had functional significance in cell cycle regulation. Our results revealed widespread novel mutations in mismatch repair deficient colorectal cancers, while Kangaroo provided a method for genome scanning to identify candidate mutation hot spots in evolution and human disease. |
