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.