Document Type : Review Article(s)
Authors
Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Tamil Nadu, India
Abstract
Gastric carcinoma, in India, is the second most prevalent cause of cancer-related deaths since most patients are asymptomatic until the disease progresses to advanced stages. Hence, there is a need for non-invasive and specific biomarkers for early screening and diagnosis.
Human mitochondrial DNA (mtDNA) has 37 genes involved in oxidative phosphorylation pathway (OxPhos). There are several 100 to 1000 mitochondria in a human cell and each mitochondrion has two to 10 copies of mtDNA. There is a significant association between the mtDNA copy number and an increase in risk of various cancers.
There is also a relation between the changes in the sequence of mtDNA in genes, such as MT-CYB, MT-ATP6 and gastric cancer, according to which the tumor cells switch to aerobic glycolysis for ATP production even in the presence of oxygen due to Warburg effect. Multiple factors have an adverse effect on mitochondrial gene expression and impairs the OxPhos pathway due to lack of sophisticated DNA repair mechanism in mitochondria.
Techniques, such as Next Generation Sequencing and Whole Genome Sequencing, are capable of early detection of copy number variants and mtDNA mutations in blood sample essential for better prognosis of gastric cancer.
Through the course of this study, various reports of a correlation between mtDNA damage and gastric cancer were analyzed and it was found that the increasing evidence of the role of mtDNA and its copy number in cancer indicates its significance as a potential biomarker for gastric cancer.
Keywords
How to cite this article:
Pramod S, Magesh S, Parvathi VD. Mitochondrial genetics in gastric cancer. Middle East J Cancer. 2022;13(1): 25-33. doi: 10.30476/mejc.2021.86726.1369.
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21. Ni Z, He J, Wu Y, Hu C, Dai X, Yan X, et al. AKT-mediated phosphorylation of ATG4B impairs mitochondrial activity and enhances the Warburg effect in hepatocellular carcinoma cells. Autophagy. 2018;14(4):685–701. doi: 10.1080/15548627.2017. 1407887.
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25. Luo S, Valencia CA, Zhang J, Lee NC, Slone J, Gui B, et al. Biparental inheritance of mitochondrial DNA in humans. Proc Natl Acad Sci. 2018;115(51):13039–44. doi:10.1073/pnas.1810946115.
26. Chinnery PF, Hudson G. Mitochondrial genetics. Br Med Bull. 2013;106(1):135-59. doi:10.1093/bmb/ ldt017.
27. Hung WY, Wu CW, Yin PH, Chang CJ, Li AFY, Chi CW, et al. Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochem Biophys Acta. 2010;1800(3):264-70. doi:10.1016/j.bbagen.2009. 06.006.
28. Bi R, Li WL, Chen MQ, Zhu Z, Yao YG. Rapid identification of mtDNA somatic mutations in gastric cancer tissues based on the mtDNA phylogeny. Mutat Res. 2011;709-10:15-20. doi:10.1016/j.mrfmmm. 2011.02.016.
29. Jiang J, Zhao JH, Wang XL, Di J, Liu ZB, Li GY, et al. Analysis of mitochondrial DNA in Tibetan gastric cancer patients at high altitude. Mol Clin Oncol. 2015;3(4):875-9. doi:10.3892/mco.2015.539.
30. Wu CW, Yin PH, Hung WY, Li AFY, Li SH, Chi CW, et al. Mitochondria DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005;44(1):19-28. doi:10.1002/gcc.20213.
31. Campa D, Barrdahl M, Santoro A, Severi G, Baglietto L, Omichessan H, et al. Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Breast Cancer Res. 2018;20(1):29. doi:10.1186/s13058-018-0955-5.
32. Tanaka T, Kobunai T, Yamamoto Y, Murono K, Otani K, Yasuda K, et al. Increased copy number variation of mtDNA in an array-based digital PCR assay predicts ulcerative colitis-associated colorectal cancer. In Vivo. 2017;31(4):713-8. doi:10.21873/invivo.11119.
33. Zhu X, Mao Y, Huang T, Yan C, Yu F, Du J, et al. High mitochondrial DNA copy number was associated with an increased gastric cancer risk in a Chinese population. Mol Carcinog. 2017;56(12):2593-600. doi:10.1002/mc.22703.
34. Rodrigues-Antunes S, Borges BN. Alterations in mtDNA, gastric carcinogenesis and early diagnosis. Mitochondrial DNA A DNA Mapp Seq Anal. 2019; 30(2):226-33. doi:10.1080/24701394.2018. 1475478.
35. Wen SL, Zhang F, Feng S. Decreased copy number of mitochondrial DNA: A potential diagnostic criterion for gastric cancer. Oncol Lett. 2013;6(4):1098-102. doi:10.3892/ol.2013.1492.
36. Lee HC, Huang KH, Yeh TS, Chi CW. Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression. World J Gastroenterol. 2014;20(14):3950-9. doi:10.3748/wjg. v20.i14.3950.
37. Lee HC, Li SH, Lin JC, Wu CC, Yeh DC, Wei YH. Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat Res. 2004;547(1-2):71-8. doi:10.1016/j.mrfmmm.2003.12.011.
38. Hung WY, Lin JC, Lee LM, Wu CW, Tseng LM, Yin PH, et al. Tandem duplication/triplication correlated with poly-cytosine stretch variation in human mitochondrial DNA D-loop region. Mutagenesis. 2008;23(2):137-42. doi:10.1093/mutage/gen002.
39. Lee HC, Wei YH. Mitochondrial DNA instability and metabolic shift in human cancers. Int J Mol Sci. 2009;10(2):674-701. doi:10.3390/ijms10020674.
40. Zhao YB, Yang HY, Zhang XW, Chen GY. Mutation in D-loop region of mitochondrial DNA in gastric cancer and its significance. World J Gastroenterol. 2005;11(21):3304-6. doi:10.3748/wjg.v11.i21.3304.
41.Doudican NA, Song B, Shadel GS, Doetsch PW. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae. Mol Cell Biol. 2005;25(12):5196-204. doi:10.1128/MCB.25.12.5196-5204.2005.
42. Graziewicz MA, Day BJ, Copeland WC. The mitochondrial DNA polymerase as a target of oxidative damage. Nucleic Acids Res. 2002;30(13):2817-24. doi:10.1093/nar/gkf392.
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