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


METHODS
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.
Okochi
Osamu
O
Second Department of Surgery, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Hibi
Kenji
K
Uemura
Takanori
T
Inoue
Soichiro
S
Takeda
Shin
S
Kaneko
Tetsuya
T
Nakao
Akimasa
A
D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial