The"modification"Type Microsatellite Change in High Frequency Microsatellite Instability Colorectal Cancer Closely Relating to MLH1 and KRAS Mutation
10.3969/j.issn.1673-6273.2008.05.023
- VernacularTitle:高频度微卫星不稳定性大肠癌"修饰型"微卫星变化与MLH1及KRAS基因突变密切相关
- Author:
Yan ZHAO
1
;
Tao ZHANG
;
Jian-Jun ZHANG
;
Zhi-Chao ZHENG
;
Yi-Liang ZHAO
;
Yoshihiko MAEHARA
;
Hui-Mian XIU
Author Information
1. 辽宁省肿瘤医院
- Keywords:
Microsatellite instability(MSI);
Rreplication errors;
DNA mismatch repair;
Mutator phenotype;
Base substitutions
- From:
Progress in Modern Biomedicine
2008;8(5):875-880
- CountryChina
- Language:Chinese
-
Abstract:
Microsatellite instability(MSI)was defined according to the frequency of positive findings in a panel of MSI markers.High frequency MSI(MSI-H)was the phenotype in which repeat sequences were extraordinarily unstable, and was considered to be the bona fide phenotype of DNA mismatch repair defection. However base substitutions in some well studied oncogenes or tumor suppressors were reported to be uncommon in MSI-H tumors. To explore this obvious contradiction, the relationship between MSI and KRAS gene mutations were studied in a panel of 76 human colorectal carcinomas, the whole exon of MLH1 and MSH2 were sequenced for MSI-H tumors. KRAS gene mutation was confirmed by similar frequencies in tumors of different MSI status. Intriguingly, all of the KRAS mutant MSI-H tumors harbored sequence alterations in MLH1gene, which was a key player in DNA mismatch repair system. This implied that in MSI-H tumors carrying MMR mutations, KRAS mutation were frequently and almost exclusively occurred. Furthermore, these MMR mutants were uniformly carrying a unique "modification" + "jumping" type MSI, which was different to MSI-H tumors without MLH1 or MSH2 gene mutations. This study shaded lights on the heterogeneity of MSI-H tumors, and implied the connection between "modification" type MSI and DNA mismatch defection.
