Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium.
Microsatellite instability (MSI) in human carcinoma DNA is a characteristic phenotype observed in hereditary non-polyposis colorectal cancer and also in some human sporadic cancers including multiple primary carcinomas. In this study, we analyzed mutations in the hCHK1, E2F4, hMSH3, and hMSH6 genes in MSI+ human cancers arising in colorectum, stomach and endometrium. The E2F4 and hMSH3 genes were mutated in all tumor types. Interestingly, the hMSH6 gene was mutated in colorectal and gastric cancers but not in endometrial cancer; this is similar to the TGFbetaRII gene. It is notable that the mutation status of the secondary mutators, hMSH3 and hMSH6, did not influence slippage-related frameshift mutations in genes harboring simple tandem-repeats, which suggests that the MSI phenotype may be affected mainly by abnormalities in the primary mutator genes, not by the secondary mutator genes. No mutations were observed in the cell cycle checkpoint gene hCHK1; mutations of this gene are thought to have a limited role, if any, in at least the tumor types analyzed in this study.
Semba
S
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Department of Molecular Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8575, Japan.
Ouyang
H
H
Han
S Y
SY
Kato
Y
Y
Horii
A
A
D000071877:Checkpoint Kinase 1; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013274:Stomach Neoplasms / Q000235:genetics*
D000071877:Checkpoint Kinase 1; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D029701:Saccharomyces cerevisiae Proteins; C078444:MSH3 protein, human; C098790:MSH6 protein, S cerevisiae; C000605867:CHEK1 protein, human; C421109:multidrug resistance-associated protein 1