Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer
- PMID: 19527772
- DOI: 10.1016/j.bbagen.2009.06.006
Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer
Abstract
Background: Somatic mutation in mitochondrial DNA (mtDNA) has been proposed to contribute to initiation and progression of human cancer. In our previous study, high frequency of somatic mutations was found in the D-loop region of mtDNA of gastric cancers. However, it is unclear whether somatic mutations occur in the coding region of mtDNA of gastric cancers.
Methods: Using DNA sequencing, we studied 31 gastric cancer specimens and corresponding non-cancerous stomach tissues. Moreover, a human gastric cancer SC-M1 cell line was treated with oligomycin to induce mitochondrial dysfunction. Cisplatin sensitivity and cell migration were analyzed.
Results: We identified eight somatic mutations in the coding region of mtDNAs of seven gastric cancer samples (7/31, 22.6%). Patients with somatic mutations in the entire mtDNA of gastric cancers did not show significant association with their clinicopathologic features. Among the eight somatic mutations, five point mutations (G3697A, G4996A, G9986A, C12405T and T13015C) are homoplasmic and three mutations (5895delC, 7472insC and 12418insA) are heteroplasmic. Four (4/8, 50%) of these somatic mutations result in amino acid substitutions in the highly conserved regions of mtDNA, which potentially lead to mitochondrial dysfunction. In addition, in vitro experiments in SC-M1 cells revealed that oligomycin-induced mitochondrial dysfunction promoted resistance to cisplatin and enhanced cell migration. N-acetyl cysteine was effective in the prevention of the oligomycin-enhanced migration, which suggests that reactive oxygen species generated by defective mitochondria may be involved in the enhanced migration of SC-M1 cells.
General significance: Our results suggest that somatic mtDNA mutations and mitochondrial dysfunction may play an important role in the malignant progression of gastric cancer.
Copyright (c) 2009 Elsevier B.V. All rights reserved.
Similar articles
-
Somatic mutations of mitochondrial genome in hepatocellular carcinoma.Mitochondrion. 2010 Mar;10(2):174-82. doi: 10.1016/j.mito.2009.12.147. Epub 2009 Dec 16. Mitochondrion. 2010. PMID: 20006738
-
Mitochondrial dysfunction promotes cell migration via reactive oxygen species-enhanced β5-integrin expression in human gastric cancer SC-M1 cells.Biochim Biophys Acta. 2012 Jul;1820(7):1102-10. doi: 10.1016/j.bbagen.2012.04.016. Epub 2012 Apr 26. Biochim Biophys Acta. 2012. PMID: 22561002
-
Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer.Genes Chromosomes Cancer. 2005 Sep;44(1):19-28. doi: 10.1002/gcc.20213. Genes Chromosomes Cancer. 2005. PMID: 15892105
-
Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression.World J Gastroenterol. 2014 Apr 14;20(14):3950-9. doi: 10.3748/wjg.v20.i14.3950. World J Gastroenterol. 2014. PMID: 24744584 Free PMC article. Review.
-
Somatic mutations of mitochondrial DNA in aging and cancer progression.Ageing Res Rev. 2010 Nov;9 Suppl 1:S47-58. doi: 10.1016/j.arr.2010.08.009. Epub 2010 Sep 8. Ageing Res Rev. 2010. PMID: 20816876 Review.
Cited by
-
The effect of somatic mutations in mitochondrial DNA on the survival of patients with primary brain tumors.Croat Med J. 2024 Apr 30;65(2):111-121. doi: 10.3325/cmj.2024.65.111. Croat Med J. 2024. PMID: 38706237 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.
-
Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.Br J Cancer. 2023 Oct;129(8):1261-1273. doi: 10.1038/s41416-023-02409-5. Epub 2023 Aug 29. Br J Cancer. 2023. PMID: 37644092 Free PMC article.
-
Role of mitochondrial alterations in human cancer progression and cancer immunity.J Biomed Sci. 2023 Jul 31;30(1):61. doi: 10.1186/s12929-023-00956-w. J Biomed Sci. 2023. PMID: 37525297 Free PMC article. Review.
-
Ribosomal DNA copy number alteration in blood sample from gastric cancer patients.Mol Biol Rep. 2023 Sep;50(9):7155-7160. doi: 10.1007/s11033-023-08630-y. Epub 2023 Jul 5. Mol Biol Rep. 2023. PMID: 37407803
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical