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Novel Mutations in Cholangiocarcinoma with Low Frequencies Revealed by Whole Mitochondrial Genome Sequencing

  • Muisuk, Kanha (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Silsirivanit, Atit (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Imtawil, Kanokwan (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Bunthot, Suphawadee (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Pukhem, Ake (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Pairojkul, Chawalit (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Wongkham, Sopit (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Wongkham, Chaisiri (Department of Biochemistry, Faculty of Medicine, Khon Kaen University)
  • Published : 2015.03.18

Abstract

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

Keywords

Biliary cancer;bile duct cancer;mitochondrial mutation;mitochondrial genome

Acknowledgement

Supported by : Khon Kaen University

References

  1. Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. (2005). High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene, 24, 1455-60. https://doi.org/10.1038/sj.onc.1208292
  2. Allalunis-Turner J, Ma I, Hanson J, Pearcey RG. (2006). mtDNA mutations in invasive cervix tumors: a retrospective analysis. Cancer lett, 243, 193-201. https://doi.org/10.1016/j.canlet.2005.11.035
  3. Anderson S, Bankier AT, Barrell BG, et al. (1981). Sequence and organization of the human mitochondrial genome. Nature, 290, 457-65. https://doi.org/10.1038/290457a0
  4. Bai Y, Attardi G. (1998). The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme. EMBO J, 17, 4848-58. https://doi.org/10.1093/emboj/17.16.4848
  5. Brandon M, Baldi P, Wallace DC. (2006). Mitochondrial mutations in cancer. Oncogene, 25, 4647-62. https://doi.org/10.1038/sj.onc.1209607
  6. Canter JA, Kallianpur AR, Parl FF, Millikan RC. (2005). Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res, 65, 8028-33.
  7. Chatterjee A, Mambo E, Sidransky D. (2006). Mitochondrial DNA mutations in human cancer. Oncogene, 25, 4663-74. https://doi.org/10.1038/sj.onc.1209604
  8. DiMauro S, Schon EA. (2003). Mitochondrial respiratory-chain diseases. N Eng J Med, 348,2656-68. https://doi.org/10.1056/NEJMra022567
  9. Fogg VC, Lanning NJ, Mackeigan JP. (2011). Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer, 30, 526-39. https://doi.org/10.5732/cjc.011.10018
  10. Gaude E, Frezza C. (2014). Defects in mitochondrial metabolism and cancer. Cancer Met, 2, 10. https://doi.org/10.1186/2049-3002-2-10
  11. Herrmann PC, Gillespie JW, Charboneau L, et al. (2003). Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer. Proteomics, 3, 1801-10. https://doi.org/10.1002/pmic.200300461
  12. Holt IJ, Harding AE, Petty RK, Morgan-Hughes JA. (1990). A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Gen, 46, 428-33.
  13. Huai JP, Ding J, Ye XH, Chen YP. (2014). Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies. Asian Pac J Cancer Prev, 15, 3477-82. https://doi.org/10.7314/APJCP.2014.15.8.3477
  14. Hung WY, Wu CW, Yin PH, et al. (2010). Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochi Biophys Acta, 1800, 264-70. https://doi.org/10.1016/j.bbagen.2009.06.006
  15. Khunluck T, Kukongviriyapan V, Puapairoj A, et al (2014). Association of NRF2 polymorphism with cholangiocarcinoma prognosis in Thai patients. Asian Pac J Cancer Prev, 15, 299-304. https://doi.org/10.7314/APJCP.2014.15.1.299
  16. Kim R, Emi M, Tanabe K. (2006). Role of mitochondria as the gardens of cell death. Cancer Chemo Pharmacol, 57, 545-53. https://doi.org/10.1007/s00280-005-0111-7
  17. Krieg RC, Knuechel R, Schiffmann E, et al. (2004). Mitochondrial proteome: cancer-altered metabolism associated with cytochrome c oxidase subunit level variation. Proteomics, 4, 2789-95. https://doi.org/10.1002/pmic.200300796
  18. Liu VW, Shi HH, Cheung AN, et al. (2001). High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer Res, 61, 5998-6001.
  19. Liu VW, Yang HJ, Wang Y, et al. (2003). High frequency of mitochondrial genome instability in human endometrial carcinomas. Brit J Cancer, 89, 697-701. https://doi.org/10.1038/sj.bjc.6601110
  20. Ma Y, Bai RK, Trieu R, Wong LJ. (2010). Mitochondrial dysfunction in human breast cancer cells and their

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