Characterization of Mutator Pathway in Younger-age-onset Colorectal Adenocarcinomas.
10.3346/jkms.2003.18.3.387
- Author:
Seon Ae ROH
1
;
Hee Cheol KIM
;
Jung Seon KIM
;
Jin Cheon KIM
Author Information
1. Department of Surgery, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Seoul, Korea. jckim@amc.seoul.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Colorectal Neoplasms;
DNA Repair;
Microsatellite Repeats;
Methylation
- MeSH:
Adenocarcinoma/*genetics;
Adult;
Age of Onset;
Colorectal Neoplasms/*genetics;
DNA Methylation;
DNA Repair/genetics;
Female;
Human;
Male;
Microsatellite Repeats;
Mutation, Missense;
Neoplasm Proteins/*genetics;
Promoter Regions (Genetics);
Prospective Studies;
Proteins/*genetics;
Registries
- From:Journal of Korean Medical Science
2003;18(3):387-391
- CountryRepublic of Korea
- Language:English
-
Abstract:
The high-frequency microsatellite instability (MSI-H) phenotype, frequently identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts for approximately 15% of sporadic colorectal cancers. Microsatellite instability (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes, i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors. The mutator pathway including microsatellite instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns were identified in 21 sporadic colorectal adenocarcinoma patients younger than 30 yr excluding HNPCC. More than half of tumors showed MSI, with five MSI-H and six MSI-L (low-frequency microsatellite instability). Three of six MSI-H tumors showed the hMLH1 promoter methylation and did not express the hMLH1 protein. On the other hand, all MSI-L and all MSS (microsatellite stable) tumors expressed both hMSH2 and hMLH1 proteins. Two novel mutations, i.e. a missense mutation in hMLH1 and a splice-site alteration in hMSH2, were identified in two patients respectively. Although mutator pathway was implicated in younger-age-onset colorectal carcinogenesis, many tumors appeared to evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in HNPCC.
