Detection of mitochondrial DNA alterations in the serum of hepatocellular carcinoma patients

Clin Cancer Res. 2002 Sep;8(9):2875-8.


Purpose: Somatic mutations in mitochondrial DNA (mtDNA) have recently been detected in various cancers. These mutations could possibly be detected in serum because mtDNA has a higher copy number than nuclear DNA. Thus, we examined genetic alterations in the D-loop region of mtDNA in hepatocellular carcinoma (HCC) patients.

Experimental design: Fifty patients with HCC were investigated in this study. Somatic mutations in the D-loop region of tumor mtDNA were screened by direct sequencing, and then the paired serum samples were investigated using mutation-specific mismatch ligation assay.

Results: Fifteen of 100 sequence variants that were detected in tumor mtDNA have not been recorded previously. True somatic mutations in the D-loop region were detected in 17 of 50 patients (34%). Subsequent screening for paired serum by mismatch ligation assay revealed that 5 of 15 paired serum samples (33%) contained the same mutations as primary tumors.

Conclusions: mtDNA mutation may be a novel tumor marker of HCC and may prove effective for detection of tumor DNA in the serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / genetics
  • DNA Mutational Analysis
  • DNA, Mitochondrial / blood*
  • DNA, Mitochondrial / genetics
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / genetics
  • Mutation*
  • Polymerase Chain Reaction / methods
  • Sequence Analysis, DNA


  • Biomarkers, Tumor
  • DNA, Mitochondrial