Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma

Hsin Chen Lee, Shu Hui Li, Jin Ching Lin, Cheng Chung Wu, Dah Cherg Yeh, Yau Huei Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

235 Scopus citations


Somatic mutations in mitochondrial DNA (mtDNA) have been detected in many human cancers, including hepatocellular carcinoma (HCC). The D-loop region was found to be a "hot spot" for mutation in mtDNA of the tumors. However, effects of the D-loop mutations on the copy number of mtDNA in tumor tissues are poorly understood. Using direct sequencing, we examined mutations in the D-loop region of mtDNA in 61 HCCs and the corresponding non-tumor liver tissues. The results revealed that 39.3% of the HCCs carried somatic mutation(s) in the D-loop of mtDNA, and most of these mutations were homoplasmic. Moreover, 37.0% (10/27) of these mutations were T-to-C and G-to-A transitions and 40.7% (11/27) of them were located in the polycytidine stretch between nucleotide position (np) 303 and 309 of mtDNA. In addition, we found that mtDNA copy number of HCC was significantly decreased in 60.5% of the patients with hepatoma, especially in those with somatic mutation(s) in the D-loop of mtDNA (17/24). This decrease in mtDNA copy number was highly associated with the occurrence of point mutations near the replication origin of the heavy-strand of mtDNA. Interestingly, we found that 42.9% (6/14) of the HCCs without mutation in the D-loop had a reduced copy number of mtDNA, indicating that other unidentified factors involved in mitochondrial biogenesis might be defective in the tumor. The results obtained in this study strongly suggest that somatic mutations in the D-loop together with the decrease in the copy number of mtDNA may be an important event during the early phase of liver carcinogenesis.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Issue number1-2
StatePublished - 22 03 2004
Externally publishedYes


  • Copy number
  • Hepatocellular carcinoma
  • Mitochondrial DNA
  • Nuclear DNA
  • Nucleotide position
  • PCR
  • Polymerase chain reaction
  • ROS
  • Reactive oxygen species
  • Somatic mutation
  • mtDNA
  • nDNA
  • np


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