J Korean Soc Coloproctol.  1998 Mar;14(1):41-49.

Microsatellite Instability and hMSH2 Gene Mutations in Sporadic Colorectal Cancers

• Jeon HM
• Oh ST
• Kim JS
• Chang SK
• Kim JS

Abstract

Microsatellites are short nucleotide repeat sequences present throughout the human genome. Alterations of microsatellites, comprising extra or missing copies of these se quences, have been termed microsatellite instability(MSI, genetic instability, replication errors, RER(+) phenotype). To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1 and hPMS2, are thought to account for the observation of microsatellite instability in tumor from Hereditary nonpolyposis colorectal cancer (HNPCC) patients. The genetic defect responsible for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be clearly delineated. The purpose of this study was to determine the presence of MSI in sporadic cancer and to correlate its occurrence with clinicopathological parameters, we have studied six microsatellite loci by use of polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. We found that 20%(9 of 46 cases) sporadic colorectal cancers showed RER at two or several loci(RER+). Microsatellite instability was associated with location of the tumor in the proximal colon 66%(6 of 9 cases) and with poorly differentiated tumor phenotype 56%(5 of 9 cases). In order to better understand the role of somatic alterations within hMSH2 in the process of colorectal tumorigenesis, we examined the most conserved regions(codon 598~789) of this gene in nine patients with MIN spotadic colorectal cancer. 6 patient of RER(+) colorectal ca. patients had a polymorphism which was a T to C base change in the intron sequence at -6 position of the splice acceptor site at the 5'end of exon 13. This particular sequence variation is a polymorphism rather than a mutation which increase cancer susceptability. These data suggest that the genetic instability is detect ed in some colorectal cancers and play an important role in the pathogenesis of sporadic colorectal cancer.

Keyword

Sporadic colorectal cancer; Microsatellite instability; hMSH2 gene

MeSH Terms

Carcinogenesis
Colon
Colorectal Neoplasms*
Colorectal Neoplasms, Hereditary Nonpolyposis
DNA Mismatch Repair
Electrophoresis, Polyacrylamide Gel
Exons
Genome, Human
Humans
Introns
Microsatellite Instability*
Microsatellite Repeats*
Phenotype
Polymerase Chain Reaction
RNA Splice Sites
RNA Splice Sites