title: Left-Sided microsatellite unstable colorectal cancers show less frequent methylation of hMLH1 and CpG island methylator phenotype than right-sided ones.
abstract: CONCLUSIONS
  We compared the methylation status of several loci between right-sided and left-sided colorectal cancers (CRCs). To the best of our knowledge, this is the first to report that left-sided CRCs show significantly less frequent methylation at several loci and CpG island methylator phenotype (CIMP) than right-sided ones.
  
  
  OBJECTIVE
  MSI CRC occurs in 10-20% of unselected series of patients with CRC. Somatic hMLH1 promoter methylation is reported to cause MSI in sporadic cases. Many researchers report that MSI CRCs are more frequently located in the right-side colon than MSS CRCs. Though the number is very small, some MSI CRCs are located in the left-side colorectum. We focused on the existence of left-sided MSI CRCs and investigated whether they arise through hMLH1 methylation as they do in right-sided ones.
  
  
  METHODS
  Thirty-eight sporadic MSI CRCs were included in the study. The methylation status of the promoter of hMLH1, p16, MINT1, 2 and 31 were examined and the proportions of methylated samples for each locus were compared.
  
  
  RESULTS
  The left-sided group showed significantly less frequent methylation in hMLH1, p16, MINT1, 2 and 31. The frequency of CIMP+ samples in the left-sided group was significantly lower than the right-sided group.
  
  
  CONCLUSIONS
  Left-sided MSI CRCs show significantly less frequent methylation of hMLH1. They also showed significantly less frequent occurrence of CIMP+ than right-sided ones. It is possible that left-sided MSI CRCs differ from the right-sided ones in the way of acquiring MSI.
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kazama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype