Analysis of the candidate target genes for mutation in microsatellite instabililty-positive cancers of the colorectum, stomach, and endometrium

Citation
S. Semba et al., Analysis of the candidate target genes for mutation in microsatellite instabililty-positive cancers of the colorectum, stomach, and endometrium, INT J ONCOL, 16(4), 2000, pp. 731-737
Citations number
34
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
10196439 → ACNP
Volume
16
Issue
4
Year of publication
2000
Pages
731 - 737
Database
ISI
SICI code
1019-6439(200004)16:4<731:AOTCTG>2.0.ZU;2-O
Abstract
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 th is study, we analyzed mutations in the hCHK1, E2F4, hMSH3, and hMSH6 genes in MSI+ human cancers arising in colorectum, stomach and endometrium. The E 2F4 and hMSH3 genes were mutated in all tumor types. Interestingly, the hMS H6 gene was mutated in colorectal and gastric cancers but not in endometria l cancer; this is similar to the TGF beta RII gene. It is notable that the mutation status of the secondary mutators, hMSH3 and hMSH6, did not influen ce slippage-related frameshift mutations in genes harboring simple tandem-r epeats, which suggests that the MSI phenotype may be affected mainly by abn ormalities in the primary mutator genes, not by the secondary mutator genes . No mutations were observed in the cell cycle checkpoint gene hCHK1; mutat ions of this gene are thought to have a limited role, if any, in at least t he tumor types analyzed in this study.