Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show microsatellite instability
. It has been also reported that telomere
shortening frequently occurs in colorectal cancers and that telomerase
is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among microsatellite instability
length, and telomerase
activity in colorectal cancers.
Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five microsatellite loci were analyzed by polymerase chain reaction. Telomere
length was examined by Southern blot analysis. Telomerase
activity was assayed by telomeric repeat amplification protocol with minor modifications.
RESULTS: Microsatellite instability
was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency microsatellite instability
tumors that showed microsatellite instability
at more than two loci exhibited remarkably short telomeres. The microsatellite instability
correlated significantly with frequency of telomere
shortening ( P
=0.0183; Fisher's exact probability test), but not with strength of telomerase
The relationship identified by this study between microsatellite instability
shortening might suggest some association between the DNA mismatch repair system and the telomere
maintenance mechanism in colorectal cancers.