Somatic mutations of mitochondrial genome in hepatocellular carcinoma
- PMID: 20006738
- DOI: 10.1016/j.mito.2009.12.147
Somatic mutations of mitochondrial genome in hepatocellular carcinoma
Abstract
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.
Similar articles
-
Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma.Mutat Res. 2004 Mar 22;547(1-2):71-8. doi: 10.1016/j.mrfmmm.2003.12.011. Mutat Res. 2004. PMID: 15013701
-
Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers.Genes Chromosomes Cancer. 2003 Jun;37(2):186-94. doi: 10.1002/gcc.10217. Genes Chromosomes Cancer. 2003. PMID: 12696067
-
Somatic mutations of the mitochondrial genome in human breast cancers.Genes Chromosomes Cancer. 2011 Oct;50(10):800-11. doi: 10.1002/gcc.20901. Epub 2011 Jul 11. Genes Chromosomes Cancer. 2011. PMID: 21748819
-
The Drosophila mitochondrial genome.Oxf Surv Eukaryot Genes. 1984;1:1-35. Oxf Surv Eukaryot Genes. 1984. PMID: 6400770 Review.
-
[Mutation of mitochondrial DNA in patients with non-alcoholic steatohepatitis].Nihon Rinsho. 2006 Jun;64(6):1095-9. Nihon Rinsho. 2006. PMID: 16768115 Review. Japanese.
Cited by
-
An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.Sci Rep. 2024 Mar 15;14(1):6348. doi: 10.1038/s41598-024-56306-9. Sci Rep. 2024. PMID: 38491051 Free PMC article.
-
Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple-negative breast cancer patients for potential biomarker development.FASEB Bioadv. 2023 Sep 8;5(10):412-426. doi: 10.1096/fba.2023-00070. eCollection 2023 Oct. FASEB Bioadv. 2023. PMID: 37810173 Free PMC article.
-
Phlorotannins: Novel Orally Administrated Bioactive Compounds That Induce Mitochondrial Dysfunction and Oxidative Stress in Cancer.Antioxidants (Basel). 2023 Sep 7;12(9):1734. doi: 10.3390/antiox12091734. Antioxidants (Basel). 2023. PMID: 37760037 Free PMC article. Review.
-
Roles of MT-ND1 in Cancer.Curr Med Sci. 2023 Oct;43(5):869-878. doi: 10.1007/s11596-023-2771-0. Epub 2023 Aug 29. Curr Med Sci. 2023. PMID: 37642864
-
Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy.J Transl Med. 2023 Jul 28;21(1):510. doi: 10.1186/s12967-023-04367-1. J Transl Med. 2023. PMID: 37507803 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical