Mitochondrial DNA Copy Number Alteration in Human Cancers
Keywords:
mitochondrial DNA copy number, cancer risk, oxidative stress, biomarkerAbstract
Mitochondrial DNA (mtDNA) lacks protective histone and comprehensive DNA repair pathways. To compromise the damage, mitochondria increase their DNA copy numbers. Although the mechanism has not been completely understood, mtDNA copy number alteration has been demonstrated to affect multiple aspects of malignant cells’ behavior. Abnormalities of mtDNA content have also been observed in various human cancers. Moreover, epidemiological studies have showed that the blood mtDNA copy number alteration is associated with the risk of several cancers. The purpose of this review is to briefly introduce several characteristics of mtDNA copy number and its potential role as a diagnostic and prognostic marker for cancer risk prediction and prevention.
References
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Larsen NB, Rasmussen M, Rasmussen LJ. Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion. Apr 2005;5(2):89-108.
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Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol. 2005;37(4):822-834.
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Clayton DA. Transcription and replication of mitochondrial DNA. Hum Reprod. 2000;15(Suppl 2):11-17.
Chang SC, Lin PC, Yang SH, Wang HS, Liang WY, Lin JK. Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations. Int J Colorectal Dis. 2009;24(6):623-628.
Singh KK, Ayyasamy V, Owens KM, Koul MS, Vujcic M. Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet. 2009;54(9):516-524.
Yin PH, Lee HC, Chau GY, et al. Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer. 2004;90(12):2390-2396.
Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97-110.
Heddi A, Faure-Vigny H, Wallace DC, Stepien G. Coordinate expression of nuclear and mitochondrial genes involved in energy production in carcinoma and oncocytoma. Biochim Biophys Acta. 1996;1316(3):203-209.
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Kusao I, Agsalda M, Troelstrup D, Villanueva N, Shiramizu B. Chemotoxicity recovery of mitochondria in non-Hodgkin lymphoma resulting in minimal residual disease. Pediatr Blood Cancer. 2008;51(2):193-197.
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Egan K, Kusao I, Troelstrup D, Agsalda M, Shiramizu B. Mitochondrial DNA in residual leukemia cells in cerebrospinal fluid in children with acute lymphoblastic leukemia. J Clin Med Res. 2010;2(5):225-229.
Chen T, He J, Shen L, et al. The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer. BMC Med Genet. 2011;12:8.
Meierhofer D, Mayr JA, Foetschl U, et al. Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma. Carcinogenesis. 2004;25(6):1005-1010.
Wu CW, Yin PH, Hung WY, et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005;44(1):19-28.
Yamada S, Nomoto S, Fujii T, et al. Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma. Eur J Surg Oncol. 2006;32(3):303-307.
Tseng LM, Yin PH, Chi CW, et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer. 2006;45(7):629-638.
Lin CS, Wang LS, Tsai CM, Wei YH. Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2008;7(6):954-958.
Fan AX, Radpour R, Haghighi MM, et al. Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer. J Cancer Res Clin Oncol. 2009;135(8):983-989.
Vivekanandan P, Daniel H, Yeh MM, Torbenson M. Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas. Mod Pathol. 2010;23(6):790-798.
Xia P, An HX, Dang CX, et al. Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer. BMC Cancer. 2009;9:454.
Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. Mitochondrial DNA. 2012;23(5):329-332.
Xing J, Chen M, Wood CG, et al. Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst. 2008;100(15):1104-1112.
Purdue MP, Hofmann JN, Colt JS, et al. A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PLoS One. 2012;7(8):e43149.
Lan Q, Lim U, Liu CS, et al. A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma. Blood. 2008;112(10):4247-4249.
Bonner MR, Shen M, Liu CS, Divita M, He X, Lan Q. Mitochondrial DNA content and lung cancer risk in Xuan Wei, China. Lung Cancer. 2009;63(3):331-334.
Hosgood HD, 3rd, Liu CS, Rothman N, et al. Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis. 2010;31(5):847-849.
Qu F, Liu X, Zhou F, et al. Association between mitochondrial DNA content in leukocytes and colorectal cancer risk: a case-control analysis. Cancer. 2011;117(14):3148-3155.
Thyagarajan B, Wang R, Barcelo H, Koh WP, Yuan JM. Mitochondrial Copy Number is Associated with Colorectal Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2012;21(9):1574-1581.
Lynch SM, Weinstein SJ, Virtamo J, et al. Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study. Cancer Prev Res (Phila). 2011;4(11):1912-1919.
Chen XJ, Butow RA. The organization and inheritance of the mitochondrial genome. Nat Rev Genet. 2005;6(11):815-825.
Scarpulla RC. Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem. 2006;97(4):673-683.
Radpour R, Fan AX, Kohler C, Holzgreve W, Zhong XY. Current understanding of mitochondrial DNA in breast cancer. Breast J. 2009;15(5):505-509.
Capps GJ, Samuels DC, Chinnery PF. A model of the nuclear control of mitochondrial DNA replication. J Theor Biol. 2003;221(4):565-583.
Shen J, Platek M, Mahasneh A, Ambrosone CB, Zhao H. Mitochondrial copy number and risk of breast cancer: a pilot study. Mitochondrion. 2010;10(1):62-68.
Larsen NB, Rasmussen M, Rasmussen LJ. Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion. Apr 2005;5(2):89-108.
Yu M. Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sci. 2011;89(3-4):65-71.
Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol. 2005;37(4):822-834.
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):71-78.
Yu M, Zhou Y, Shi Y, et al. Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life. 2007;59(7):450-457.
Yu M, Wan Y, Zou Q. Decreased copy number of mitochondrial DNA in Ewing's sarcoma. Clin Chim Acta. May 2 2010;411(9-10):679-683.
Clayton DA. Transcription and replication of mitochondrial DNA. Hum Reprod. 2000;15(Suppl 2):11-17.
Chang SC, Lin PC, Yang SH, Wang HS, Liang WY, Lin JK. Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations. Int J Colorectal Dis. 2009;24(6):623-628.
Singh KK, Ayyasamy V, Owens KM, Koul MS, Vujcic M. Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet. 2009;54(9):516-524.
Yin PH, Lee HC, Chau GY, et al. Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer. 2004;90(12):2390-2396.
Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97-110.
Heddi A, Faure-Vigny H, Wallace DC, Stepien G. Coordinate expression of nuclear and mitochondrial genes involved in energy production in carcinoma and oncocytoma. Biochim Biophys Acta. 1996;1316(3):203-209.
Kim MM, Clinger JD, Masayesva BG, et al. Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions. Clin Cancer Res. 2004;10(24):8512-8515.
Wang Y, Liu VW, Xue WC, Tsang PC, Cheung AN, Ngan HY. The increase of mitochondrial DNA content in endometrial adenocarcinoma cells: a quantitative study using laser-captured microdissected tissues. Gynecol Oncol. 2005;98(1):104-110.
Mambo E, Chatterjee A, Xing M, et al. Tumor-specific changes in mtDNA content in human cancer. Int J Cancer. 2005;116(6):920-924.
Wang Y, Liu VW, Xue WC, Cheung AN, Ngan HY. Association of decreased mitochondrial DNA content with ovarian cancer progression. Br J Cancer. 2006;95(8):1087-1091.
Mizumachi T, Muskhelishvili L, Naito A, et al. Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells. Prostate. 2008;68(4):408-417.
Kusao I, Agsalda M, Troelstrup D, Villanueva N, Shiramizu B. Chemotoxicity recovery of mitochondria in non-Hodgkin lymphoma resulting in minimal residual disease. Pediatr Blood Cancer. 2008;51(2):193-197.
Lin CS, Chang SC, Wang LS, et al. The role of mitochondrial DNA alterations in esophageal squamous cell carcinomas. J Thorac Cardiovasc Surg. 2010;139(1):189-197 e184.
Egan K, Kusao I, Troelstrup D, Agsalda M, Shiramizu B. Mitochondrial DNA in residual leukemia cells in cerebrospinal fluid in children with acute lymphoblastic leukemia. J Clin Med Res. 2010;2(5):225-229.
Chen T, He J, Shen L, et al. The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer. BMC Med Genet. 2011;12:8.
Meierhofer D, Mayr JA, Foetschl U, et al. Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma. Carcinogenesis. 2004;25(6):1005-1010.
Wu CW, Yin PH, Hung WY, et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005;44(1):19-28.
Yamada S, Nomoto S, Fujii T, et al. Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma. Eur J Surg Oncol. 2006;32(3):303-307.
Tseng LM, Yin PH, Chi CW, et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer. 2006;45(7):629-638.
Lin CS, Wang LS, Tsai CM, Wei YH. Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2008;7(6):954-958.
Fan AX, Radpour R, Haghighi MM, et al. Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer. J Cancer Res Clin Oncol. 2009;135(8):983-989.
Vivekanandan P, Daniel H, Yeh MM, Torbenson M. Mitochondrial mutations in hepatocellular carcinomas and fibrolamellar carcinomas. Mod Pathol. 2010;23(6):790-798.
Xia P, An HX, Dang CX, et al. Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer. BMC Cancer. 2009;9:454.
Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. Mitochondrial DNA. 2012;23(5):329-332.
Xing J, Chen M, Wood CG, et al. Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst. 2008;100(15):1104-1112.
Purdue MP, Hofmann JN, Colt JS, et al. A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PLoS One. 2012;7(8):e43149.
Lan Q, Lim U, Liu CS, et al. A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma. Blood. 2008;112(10):4247-4249.
Bonner MR, Shen M, Liu CS, Divita M, He X, Lan Q. Mitochondrial DNA content and lung cancer risk in Xuan Wei, China. Lung Cancer. 2009;63(3):331-334.
Hosgood HD, 3rd, Liu CS, Rothman N, et al. Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis. 2010;31(5):847-849.
Qu F, Liu X, Zhou F, et al. Association between mitochondrial DNA content in leukocytes and colorectal cancer risk: a case-control analysis. Cancer. 2011;117(14):3148-3155.
Thyagarajan B, Wang R, Barcelo H, Koh WP, Yuan JM. Mitochondrial Copy Number is Associated with Colorectal Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2012;21(9):1574-1581.
Lynch SM, Weinstein SJ, Virtamo J, et al. Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study. Cancer Prev Res (Phila). 2011;4(11):1912-1919.
Published
2013-01-31
How to Cite
Meng, S., & Han, J. (2013). Mitochondrial DNA Copy Number Alteration in Human Cancers. North American Journal of Medicine and Science, 6(1). Retrieved from https://najms.com/index.php/najms/article/view/163
Issue
Section
Review
