Relationship between microsatellite instability and telomere shortening in colorectal cancer.
OBJECTIVE
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, telomere length, and telomerase activity in colorectal cancers.


METHODS
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 activity.


CONCLUSIONS
The relationship identified by this study between microsatellite instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.
Takagi
S
S
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Kinouchi
Y
Y
Hiwatashi
N
N
Nagashima
F
F
Chida
M
M
Takahashi
S
S
Negoro
K
K
Shimosegawa
T
T
Toyota
T
T
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology* / Q000648:ultrastructure
D004273:DNA, Neoplasm; D019098:Telomerase