title: Identification of novel genes with somatic frameshift mutations within coding mononucleotide repeats in colorectal tumors with high microsatellite instability.
abstract: We have systematically retrieved genes with coding mononucleotide repeats from sequence databases and analyzed them for mutations in tumors with high levels of microsatellite instability (MSI-H). We found somatic frameshift mutations in 7/13 genes previously not analyzed in MSI-H tumors. According to the frequency of mutations in MSI-H tumors, these genes could be divided into genes with high coding mononucleotide repeat instability (CMRI-H) and genes with low coding mononucleotide instability (CMRI-L). CMR-H genes were mutated in more than 9/38 and CMRI-L in less than 4/38 of MSI-H tumors. Four genes in our study were CMRI-H and could thus possibly play a role in the development of MSI-H tumors: TFE3 (9/38), TEF4 (12/38), RGS12 (11/38), and TCF1 (12/38). Our results suggest that systematic identification of genes with CMR in the sequence databases and determination of mutation frequency in MSI-H tumors might be a powerful tool for identification of new molecular targets in the development of MSI-H tumors.
authors.affiliation: Laboratory of Molecular Genetics, Institute of Pathology, Medical Faculty, Ljubljana, Slovenia.
authors.forename: Uros
authors.initials: U
authors.lastname: Potocnik
authors.forename: Damjan
authors.initials: D
authors.lastname: Glavac
authors.forename: Metka
authors.initials: M
authors.lastname: Ravnik-Glavac
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D030541:Databases, Genetic; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics*
chemical_list: D009711:Nucleotides