Relationship between microsatellite instability and telomere shortening incolorectal cancer

PURPOSE: Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers a rising through the replication error pathway, like most hereditary nonpolyp osis colorectal cancers, show microsatellite instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers a nd that telomerase is often activated strongly in them. The aim of this stu dy was to examine whether any relationships can be found among microsatelli te instability, telomere length, and telomerase activity in colorectal canc ers. METHODS: Genomic DNA was extracted from 55 invasive cancers and corres ponding normal mucosas. Five microsatellite loci were analyzed by polymeras e chain reaction. Telomere length was examined by Southern blot analysis. T elomerase activity was assayed by telomeric repeat amplification protocol w ith minor modifications. RESULTS: Microsatellite instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furth ermore, four high-frequency microsatellite instability tumors that showed m icrosatellite instability at more than two loci exhibited remarkably short telomeres. The microsatellite instability correlated significantly with fre quency of telomere shortening (P = 0.0183; Fisher's exact probability test) , but not with strength of telomerase activity. CONCLUSION: The relationshi p identified by this study between microsatellite instability and telomere shortening might suggest some association between the DNA mismatch repair s ystem and the telomere maintenance mechanism in colorectal cancers.