title: Lack of frameshift mutations at coding mononucleotide repeats in hepatocellular carcinoma in Japanese patients.
abstract: BACKGROUND
  Microsatellite instability occurs frequently in hereditary nonpolyposis colorectal carcinoma, in sporadic gastrointestinal carcinoma, and in other tumors. In these tumors, slippage-related frameshift mutations have been detected at coding mononucleotide repeats in genes such as those for transforming growth factor-beta receptor type II (TGFbetaRII), mannose 6-phosphate/insulinlike growth factor II receptor (M6P/IGFIIR), hMSH3, hMSH6, and Bcl-2-associated X protein (BAX). Because these genes regulate cell growth or repair DNA mismatches, loss of their function is thought to promote tumor development. The authors screened for these frameshift mutations and investigated the incidence of microsatellite instability (MI) in hepatocellular carcinoma (HCC) in Japan.
  
  
  METHODS
  Fifty HCC samples were analyzed in this study. The authors used polymerase chain reactions to screen for frameshift mutation at the TGFbetaRII (A)(10) tract, the M6P/IGFIIR (G)(8) tract, the hMSH3 (A)(8) tract, the hMSH6 (C)(8) tract, and the BAX (G)(8) tract. For MI analysis, matched tumor and nontumor liver DNA were investigated with respect to 10 microsatellite loci.
  
  
  RESULTS
  No frameshift mutation was detected in any case, and only 4% of these cancers exhibited MI in comparisons between tumor and nontumor liver specimens.
  
  
  CONCLUSIONS
  This study suggests that frameshift mutation at coding mononucleotide repeats within TGFbetaRII, M6P/IGFIIR, hMSH3, hMSH6, and BAX genes did not seem to be involved in hepatocarcinogenesis in the Japanese population studied.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Saeki
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Kiso
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: I
authors.initials: I
authors.lastname: Yabuuchi
authors.forename: S
authors.initials: S
authors.lastname: Kawata
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II