미토콘드리아의 D-고리의 다형성과 복제수와의 관계
Association between Mitochondrial D-loop Polymorphism and Copy Number
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종양의 미토콘드리아에는 유전자 돌연변이나 다형성과 같은 유전적 불안정성이 높게 나타나며, 특히D-고리에서 흔히 발견되는데 이는 암의 예후와 연관이 있다고 한다. 또한 D-고리의 유전자변이는 미토콘드리아의 복제수의 변화와 연관이 있다고 한다. 본 연구에서는 미토콘드리아 DNA의 D-고리에서 자주 나타나는 다형성인 D310과 D514의 빈도를 108명의 정상인 말초혈액 DNA에서 살펴보고 이에 따른 미토콘드리아 복제수의변화를 조사하였다. D310의 다형성은 C7은 40명(37.7%), C8은 34명(32.1%) 그리고 C9는 32명(30.2%)에서 각각 나타났다. D514의 다형성은 (CA)5와 (CA)4에서 각각 62명(61.4%)과 39명(38.6%)에서 나타났다. 미토콘드리아 복제수는 44명(40.7%)에서 증가되어 있었고, 64명(59.3%)에서 감소가 관찰되었다. D310과 D514의 다형성과 복제수의 변화의 증가와 감소와의 상관관계는 없었다. 정상인에서 미토콘드리아 D-고리의 다형성과 복제수와는 연관성은 없었으나, 이를 바탕으로 다양한 질환에서 이들 미토콘드리아 표지자들의 변화를 조사할 필요가있을 것이다.
Abstract
Mitochondria in cancer have genetic instability like genetic mutations or polymorphisms, and D-loopis hot spot region and is suggested its association with cancer prognosis. Genetic variations of D-loop were associatedwith mitochondrial copy number. In present study, mitochondrial polymorphism in D-loop (D310 and D514)was studied in 108 DNAs from health individuals and its association with mitochondrial copy number was alsoinvestigated. In D310 polymorphism, C7 was most common (37.7%, 40/108), and C8 and C9 was found in 32.1%and 30.2%, respectively. In D514 polymorphism, (CA)5 and (CA)4 was shown in 61.4% and 38.6%, respectively. Mitochondrial copy number was increased in 40.7% while it was decreased in 59.3%. There was no associationbetween mitochondrial polymorphism and copy number. Follow-up study should be needed to confirm its changein same individuals.
참고문헌 (32)
- Attardi G, "Biogenesis of mitochondria", Annu Rev Cell Biol, 4, pp.289~333 (1998)
- Anderson S, "Sequence and organization of the human mitochondrial genome", Nature, 290, pp.457~465 (1981)
- Wallace DC, "Diseases of the mitochondrial DNA", Annu Rev Biochem, 61, pp.1175~1212 (1992)
- Wallace DC, "Mitochondrial DNA sequence variation in human evolution and disease", Proc Natl Acad Sci USA, 91, pp.8739~8746 (1994)
- Penta JS, "Mito-chondrial DNA in human malignancy", Mutat Res, 488, pp.119~133 (2001)
- Mandavilli BS, "Mitochondrial DNA repair and aging", Mutat Res, 509, pp.127~151 (2002)
- Lièvre A, "Clinical value of mitochondrial mutations in colorectal cancer", J Clin Oncol, 23, pp.3517~3525 (2005)
- Van Tuyle GC, "A compact form of rat liver mitochondrial DNA stabilized by bound proteins", J Biol Chem, 254, pp.6044~6053 (1979)
- Corral-Debrinski M, "Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age", Nat Genet, 2, pp.324~329 (1992)
- Clay Montier LL, "Number matters: control of mammalian mitochondrial DNA copy number", J Genet Genomics, 36, pp.125~131 (2009)
- Kim MM, "Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions", Clin Cancer Res, 10, pp.8512~8515 (2004)
- Wang Y, "Association of decreased mitochondrial DNA content with ovarian cancer progression", Br J Cancer, 95, pp.1087~1091 (2006)
- Lin CS, "The role of mitochondrial DNA alterations in esophageal squamous cell carcinomas", J Thorac Cardiovasc Surg, 139, pp.189~197 (2010)
- Lee HC, "Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma", Mutat Res, 547, pp.71~78 (2004)
- Wu CW, "Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer", Genes Chromosomes Cancer, 44, pp.19~28 (2005)
- Yamada S, "Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma", Eur J Surg Oncol, 32, pp.303~307 (2006)
- Yu M, "Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients", IUBMB Life, 59, pp.450~457 (2007)
- Xing J, "Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma", J Natl Cancer Inst, 100, pp.1104~1112 (2008)
- Sanchez-Cespedes M, "Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors", Cancer Res, 61, pp.7015~7019 (2001)
- Jeng JY, "Maintenance of mitochondrial DNA copy number and expression are essential for preservation of mitochondrial function and cell growth", J Cell Biochem, 103, pp.347~357 (2008)
- [URL]
- Bodenteich A, "Dinucleotide repeat in the human mitochondrial D-loop. Hum Mol Genet", 1992;, 1, pp.140~ (1992)
- Lee HC, "Mitochondrial genome instability and mtDNA depletion in human cancers", Ann NY Acad Sci, 1042, pp.109~122 (2005)
- Schwartz S Jr, "Mutational dynamic in human tumors confirms the neutral intrinsic instability of the mitochondrial D-loop polycytidine repeat", Genes Chromosom Cancer, 45, pp.770~780 (2006)
- Kose K, "Somatic mutations of mitochondrial DNA in digestive tract cancers", J Gastroenterol Hepatol, 20, pp.1679~1684 (2005)
- Chang SC, "Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations", Int J Colorectal, 24, pp.623~628 (2009)
- Szibor R, "Mitochondrial D-loop 3′ (CA)n repeat polymorphism:optimization of analysis and population data", Electrophoresis, 18, pp.2857~2860 (1997)
- Hoppeler H, "Response of skeletal muscle mitochondria to hypoxia", Exp Physiol, 88, pp.109~119 (2003)
- Weitzel JM, "Regulation of mitochondrial biogenesis by thyroid hormone", Exp Physiol, 88, pp.121~128 (2003)
- Short KR, "Decline in skeletal muscle mitochondrial function with aging in humans", Proc Natl Acad Sci USA, 102, pp.5618~5623 (2005)
- Shen J1, "Mitochondrial copy number and risk of breast cancer: a pilot study", wMitochondrion, 10, pp.62~68 (2010)
- Hosgood HD 3rd1, "Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study", Carcinogenesis, 31, pp.847~849 (2010)