title: Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability.
abstract: Frameshift mutations in genes containing mononucleotide repeats are often observed in cancers exhibiting a high frequency of microsatellite instability (MSI-H). Several tumor types, including colorectal, gastric, and endometrial carcinomas, display this phenotype in a significant proportion of cases. We recently showed in a large series of MSI-H colorectal tumors that approximately 40% of them exhibited frameshift mutations in an (A)9 tract within the coding region of the TCF-4 gene, a crucial member of the APC/beta-catenin/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 primary tumors and cell lines were found to have a 1 bp deletion in the TCF-4 repeat. In the same series of tumors we also looked for frameshift mutations in other coding repeats localized within the TGF beta-RII, BAX, IGFIIR, hMSH3 and hMSH6 genes. Our results suggest that the TCF-4 gene, in a similar manner to some of these latter genes, is differentially altered in MSI-H tumors from different primary sites.
authors.affiliation: INSERM U434-CEPH, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Duval
authors.forename: B
authors.initials: B
authors.lastname: Iacopetta
authors.forename: G N
authors.initials: GN
authors.lastname: Ranzani
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Hamelin
mesh_terms: D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics*; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors