title: Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) mutations are found in many kinds of human cancer. The aim of this study was to evaluate the relationship between mtDNA mutations in the liver and human hepatocarcinogenesis.
  
  
  METHODS
  Direct sequencing of mtDNA was done in 54 hepatocellular carcinomas (HCCs) and 47 surrounding liver tissue samples, obtained from 54 patients with HCC, and in 5 liver samples without inflammation, obtained from 5 patients with metastatic liver tumors. We also examined p53 mutations in the 54 HCCs to examine the correlation between nuclear DNA mutations and mtDNA mutations.
  
  
  RESULTS
  Mutations of mtDNA in the D-loop region were found in both HCC and noncancerous liver tissue. In normal liver without chronic inflammation, no mtDNA mutation was detected. In every case, the number of mtDNA mutations in HCC correlated with that in noncancerous liver tissue. Twelve of 52 mutation sites in the D-loop region of mtDNA were specific for HCC. The mean number of mtDNA mutations was 1.7 in well-differentiated HCC, as compared with 4.5 in moderately differentiated HCC and 4.6 in poorly differentiated HCC. The frequency of mtDNA mutations was thus higher in less differentiated HCC. We detected p53 mutations in 15 (28%) of 54 HCCs. The mean number of mtDNA mutations was 5.3 in HCC with p53 mutations and 3.8 in HCC with wild-type p53 (P = 0.024).
  
  
  CONCLUSIONS
  A higher frequency of mtDNA mutations was found in less differentiated HCCs, and it is also possible that mtDNA mutations are related to nuclear DNA mutations in HCC. The accumulation of mtDNA mutations is a useful predictor of hepatocarcinogenesis.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Koh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hirohashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D016159:Tumor Suppressor Protein p53