title: Relationship between microsatellite instability and telomere shortening in colorectal cancer.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: N
authors.initials: N
authors.lastname: Hiwatashi
authors.forename: F
authors.initials: F
authors.lastname: Nagashima
authors.forename: M
authors.initials: M
authors.lastname: Chida
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Negoro
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D019098:Telomerase