Articles

Mutation Screening in the Mitochondrial D-Loop Region of Tumoral and Non-tumoral Breast Cancer in Iranian Patients

Abstract

The mitochondrial DNA (mtDNA) mutations in mitochondrial coding and non coding regions seem to be important in carcinogenesis. The aim of this investigation was to evaluate coding region (mt-tRNAPhe and tRNAPro) and non-coding sequence, mitochondrial displacement loop (mtDNA D-loop), in the cancerous and non-cancerous lesions of Iranian patients with breast cancer (BC). Genomic DNA was extracted from 50 breast tumors and surrounding normal tissue pairs as well as from 50 unrelated normal breast tissues from Iranian Kurdish population. Subsequently, PCR amplification was performed using specific primers, and then PCR products were subjected to direct sequencing. 41 genetic variants were identified in mtDNA D-loop among tumoral and non-tumoral tissues but not in tRNAPhe and tRNAPro sequences. Our findings indicated that C182T, 194insT, 285insA and 16342delT were just found in BC tumors whereas 302insC, C309T and C16069T found in both tumors and surrounding normal tissues. Although our findings showed that the observed genetic variations were not restricted to breast cancer tissues, some genetic changes were found only in BC tumors. Our results, in agreement with the evidence from earlier studies, confirm that the mtDNA genetic alterations might be implicated in tumor initiation, progression and development.

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61(2):69-90.

Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F. Chemoprevention for breast cancer. Cancer Treat Rev 2012;38(5):329-39.

Lillie SE, Brewer NT, O'Neill SC, Morrill EF, Dees EC, Carey LA, Rimer BK. Retention and use of breast cancer recurrence risk information from genomic tests: the role of health literacy. Cancer Epidemiol Biomarkers Prev 2007;16(2):249-55.

Chan K, Morris GJ. Chemoprevention of breast cancer for women at high risk. Semin Oncol 2006;33(6):642-6.

Wang F, Fang Q, Ge Z, Yu N, Xu S, Fan X. Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review. Mol Biol Rep 2012;39(3):2109-18.

Yu M, Shi Y, Zhang F, Zhou Y, Yang Y, Wei X, Zhang L, Niu R. Sequence variations of mitochondrial DNA Dloop region are highly frequent events in familial breast cancer. J Biomed Sci 2008;15(4):535-43.

Kulawiec M, Owens KM, Singh KK. Cancer cell mitochondria confer apoptosis resistance and promote metastasis. Cancer Biol Ther 2009;8(14):1378-85.

Larsson NG, Clayton DA. Molecular genetic aspects of human mitochondrial disorders. Annu Rev Genet 1995;29:151-78.

Nagley P, Wei YH. Ageing and mammalian mitochondrial genetics. Trends Genet 1998;14(12):513-7.

de Souza-Pinto NC, Mason PA, Hashiguchi K, Weissman L, Tian J, Guay D, Lebel M, Stevnsner TV, Rasmussen LJ, Bohr VA. Novel DNA mismatch-repair activity involving YB-1 in human mitochondria. DNA Repair (Amst) 2009;8(6):704-19.

Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG. Sequence and organization of the human mitochondrial genome. Nature 1981;290(5806):457-65.

Kulawiec M, Safina A, Desouki MM, Still I, Matsui S, Bakin A, Singh KK. Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion. Cancer Biol Ther 2008;7(11):1732-43.

Yu M, Zhou Y, Shi Y, Ning L, Yang Y, Wei X, Zhang N, Hao X, Niu R. Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis inm Chinese breast cancer patients. IUBMB Life 2007;59(7):450-7.

Mambo E, Chatterjee A, Xing M, Tallini G, Haugen BR, Yeung SC, Sukumar S, Sidransky D. Tumor-specificchanges in mtDNA content in human cancer. Int J Cancer 2005;116(6):920-4.

Lee HC, Yin PH, Lin JC, Wu CC, Chen CY, Wu CW, Chi CW, Tam TN, Wei YH. Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci 2005;1042:109-22.

Tseng LM, Yin PH, Chi CW, Hsu CY, Wu CW, Lee LM, Wei YH, Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer 2006;45(7):629-38.

Desouki MM, Kulawiec M, Bansal S, Das GM, Singh KK. Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors. Cancer Biol Ther 2005;4(12):1367-73.

Mizumachi T, Muskhelishvili L, Naito A, Furusawa J, Fan CY, Siegel ER, Kadlubar FF, Kumar U, Higuchi M. Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells. Prostate 2008;68(4):408-17.

Selvanayagam P, Rajaraman S. Detection of mitochondrial genome depletion by a novel cDNA in renal cell carcinoma. Lab Invest 1996;74(3):592-9.

Yin PH, Lee HC, Chau GY, Wu YT, Li SH, Lui WY, Wei YH, Liu TY, Chi CW. Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer 2004;90(12):2390-6.

Lièvre A, Blons H, Houllier AM, Laccourreye O, Brasnu D, Beaune P, Laurent-Puig P. Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma. Br J Cancer 2006;94(5):692-7.

Tong BC, Ha PK, Dhir K, Xing M, Westra WH, Sidransky D, Califano JA. Mitochondrial DNA alterations in thyroid cancer. J Surg Oncol 2003;82(3):170-3.

Wu CW, Yin PH, Hung WY, Li AF, Li SH, Chi CW, Wei YH, Lee HC. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer 2005;44(1):19-28.

Weber K, Ridderskamp D, Alfert M, Hoyer S, Wiesner RJ. Cultivation in glucose-deprived medium stimulates mitochondrial biogenesis and oxidative metabolism in HepG2 hepatoma cells. Biol Chem 2002;383(2):283-90.

Espineda CE, Chang JH, Twiss J, Rajasekaran SA, Rajasekaran AK. Repression of Na,K-ATPase beta1- subunit by the transcription factor snail in carcinoma. Mol Biol Cell 2004;15(3):1364-73.

Isidoro A, Martínez M, Fernández PL, Ortega AD, Santamaría G, Chamorro M, Reed JC, Cuezva JM. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 2004;378(Pt 1):17-20.

Eng C, Kiuru M, Fernandez MJ, Aaltonen LA. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 2003;3(3):193-202.

Modica-Napolitano JS, Kulawiec M, Singh KK. Mitochondria and human cancer. Curr Mol Med 2007;7(1):121-31.

Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene 2006;25(34):4647-62.

Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005;65(17):8028-33.

Suzuki M, Toyooka S, Miyajima K, Iizasa T, Fujisawa T, Bekele NB, Gazdar AF. Alterations in the mitochondrialdisplacement loop in lung cancers. Clin Cancer Res 2003;9(15):5636-41.

Lièvre A, Chapusot C, Bouvier AM, Zinzindohoué F, Piard F, Roignot P, Arnould L, Beaune P, Faivre J, Laurent-Puig P. Clinical value of mitochondrial mutationsin colorectal cancer. J Clin Oncol 2005;23(15):3517-25.

Ye C, Shu XO, Pierce L, Wen W, Courtney R, Gao YT, Zheng W, Cai Q. Mutations in the mitochondrial DNA Dloop region and breast cancer risk. Breast Cancer Res Treat 2010;119(2):431-6.

Kuo SJ, Chen M, Ma GC, Chen ST, Chang SP, Lin WY, Chen YC, Lee TH, Lin TT, Liu CS. Number of somatic mutations in the mitochondrial D-loop region indicates poor prognosis in breast cancer, independent of TP53 mutation. Cancer Genet Cytogenet 2010;201(2):94-101.

Zhu W, Qin W, Bradley P, Wessel A, Puckett CL, SauterER. Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis 2005;26(1):145-52.

Tan DJ, Bai RK, Wong LJ. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer.Cancer Res 2002;62(4):972-6.

Alazzouzi H, Farriol M, Espín E, Armengol M, Pena M, Zeh K, Schwartz S, Schwartz S Jr. Molecular patterns of nuclear and mitochondrial microsatellite alterations in breast tumors. Oncol Rep 2003;10(5):1561-7.

Pavicic WH, Laguens M, Richard SM. Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer. Mol Med 2009;15(5-6):160-5.

Deschauer M, Swalwell H, Strauss M, Zierz S, Taylor RW. Novel mitochondrial transfer RNA(Phe) gene mutation associated with late-onset neuromuscular disease. Arch Neurol 2006;63(6):902-5.

Hanna MG, Nelson IP, Morgan-Hughes JA, Wood NW. MELAS: a new disease associated mitochondrial DNA mutation and evidence for further genetic heterogeneity. J Neurol Neurosurg Psychiatry 1998;65(4):512-7.

Mancuso M, Filosto M, Mootha VK, Rocchi A, Pistolesi S, Murri L, DiMauro S, Siciliano G. A novel mitochondrial tRNAPhe mutation causes MERRFsyndrome. Neurology 2004;62(11):2119-21.

Moslemi AR, Lindberg C, Toft J, Holme E, Kollberg G,Oldfors A. A novel mutation in the mitochondrial tRNA(Phe) gene associated with mitochondrial myopathy. Neuromuscul Disord 2004;14(1):46-50.

Darin N, Kollberg G, Moslemi AR, Tulinius M, Holme E,Grönlund MA, Andersson S, Oldfors A. Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a sporadic patient with a G583A mutation in the mt tRNA(phe) gene. Neuromuscul Disord 2006;16(8):504-6.

Chinnery PF, Johnson MA, Taylor RW, Lightowlers RN, Turnbull DM. A novel mitochondrial tRNAphenylalanine mutation presenting with acute rhabdomyolysis. Ann Neurol 1997;41(3):408-10.

Kleinle S, Schneider V, Moosmann P, Brandner S,Krähenbühl S, Liechti-Gallati S. A novel mitochondrialtRNA(Phe) mutation inhibiting anticodon stem formation associated with a muscle disease. Biochem Biophys Res Commun 1998;247(1):112-5.

Moraes CT, Ciacci F, Bonilla E, Ionasescu V, Schon EA, DiMauro S. A mitochondrial tRNA anticodon swap associated with a muscle disease. Nat Genet 1993;4(3):284-8.

Sanchez-Cespedes M, Parrella P, Nomoto S, Cohen D, Xiao Y, Esteller M, Jeronimo C, Jordan RC, Nicol T, Koch WM, Schoenberg M, Mazzarelli P, Fazio VM, Sidransky D. Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res 2001;61(19):7015-9.

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IssueVol 50, No 7 (2012) QRcode
SectionArticles
Keywords
Breast Cancer D-loop tRNAPhe tRNAPro

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How to Cite
1.
Rahmani B, Azimi C, Omranipour R, Raoofian R, Zendehdel K, Saee-Rad S, Heidari M. Mutation Screening in the Mitochondrial D-Loop Region of Tumoral and Non-tumoral Breast Cancer in Iranian Patients. Acta Med Iran. 1;50(7):447-453.