Somatic mutations have been identified in
mitochondrial DNA (
mtDNA) of various human primary
cancers. However, their roles in the pathophysiology of
cancers are still unclear. In our previous study, high frequency of somatic mutations was found in the D-loop region of
mtDNA of
hepatocellular carcinomas (HCCs). In the present study, we examined 44 HCCs and corresponding non-cancerous liver tissues, and identified 13 somatic mutations in the coding region of mtDNAs from 11 HCC samples (11/44, 25%). Among the 13
mtDNA mutations, six mutations (T6787C, G7976A, A9263G, G9267A, A9545G and A11708G) were homoplasmic while seven mutations (956delC, T1659C, G3842A, G5650A, 11032delA, 12418insA and a 66bp deletion) were heteroplasmic. Moreover, the G3842A transition created a
premature stop codon and the 66bp deletion could omit 22
amino acid residues in the
NADH dehydrogenase (ND) subunit 1 (ND1) gene. The 11032delA and 12418insA could result in frame-shift mutation in the ND4 and ND5 genes, respectively. The T1659C transition in
tRNA(Val) gene and G5650A in
tRNA(Ala) gene were reported to be clinically associated with some
mitochondrial disorders. In addition, the T6787C (
cytochrome c oxidase subunit I, COI), G7976A (COII), G9267A (COIII) and A11708G (ND4) mutations could result in amino acid substitutions in the highly conserved regions of the affected mitochondrial genes. These
mtDNA mutations (10/13, 76.9%) have the potential to cause
mitochondrial dysfunction in HCCs. Taken these results together, we suggest that there may be a higher frequency of
mtDNA mutations in HCC than in normal liver tissues from the same individuals.