DOI QR코드

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Mitochondrial Genome Microsatellite Instability and Copy Number Alteration in Lung Carcinomas

  • Dai, Ji-Gang (Department of Thoracic Cardiovascular Surgery of Xinqiao Hospital, the Third Military Medical University) ;
  • Zhang, Zai-Yong (Department of Thoracic Cardiovascular Surgery of Xinqiao Hospital, the Third Military Medical University) ;
  • Liu, Quan-Xing (Department of Thoracic Cardiovascular Surgery of Xinqiao Hospital, the Third Military Medical University) ;
  • Min, Jia-Xin (Department of Thoracic Cardiovascular Surgery of Xinqiao Hospital, the Third Military Medical University)
  • 발행 : 2013.04.30

초록

Objective: Mitochondrial DNA (mtDNA) is considered a hotspot of mutations in various tumors. However, the relationship between microsatellite instability (MSI) and mtDNA copy number alterations in lung cancer has yet to be fully clarifieds. In the current study, we investigated the copy number and MSI of mitochondrial genome in lung carcinomas, as well as their significance for cancer development. Methods: The copy number and MSI of mtDNA in 37 matched lung carcinoma/adjacent histological normal lung tissue samples were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assays for sequence variation, followed by sequence analysis and fluorogenic 5'-nuclease real-time PCR. Student's t test and linear regression analyses were employed to analyze the association between mtDNA copy number alterations and mitochondrial MSI (mtMSI). Results: The mean copy number of mtDNA in lung carcinoma tissue samples was significantly lower than that of the adjacent histologically normal lung tissue samples (p<0.001). mtMSI was detected in 32.4% (12/37) of lung carcinoma samples. The average copy number of mtDNA in lung carcinoma samples containing mtMSI was significantly lower than that in the other lung carcinoma samples (P<0.05). Conclusions: Results suggest that mtMSI may be an early and important event in the progression of lung carcinogenesis, particularly in association with variation in mtDNA copy number.

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참고문헌

  1. Amuthan G, Biswas G, Ananadatheerthavarada HK, et al (2002). Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. Oncogene, 21, 7839-49. https://doi.org/10.1038/sj.onc.1205983
  2. Augenlicht LH, Heerdt BG (2001). Mitochondria: integrators in tumorigenesis? Nat Genet, 28, 104-5. https://doi.org/10.1038/88800
  3. Bendall KE, Sykes BC(1995). Length heteroplasmy in the first hypervariable segment of the human mtDNA control region. Am J Hum Genet, 57, 248-56.
  4. Bianchi NO, Bianchi MS, Richard SM (2001). Mitochondrial genome instability in human cancers. Mutat Res, 488, 9-23. https://doi.org/10.1016/S1383-5742(00)00063-6
  5. Clay Montier LL, Deng JJ, Bai Y (2009). Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics, 36, 125-31. https://doi.org/10.1016/S1673-8527(08)60099-5
  6. Guerra F, Kurelac I, Cormio A, et al (2011). Placing mitochondrial DNA mutations within the progression model of type I endometrial carcinoma. Hum Mol Genet, 20, 2394-405. https://doi.org/10.1093/hmg/ddr146
  7. Guerra F, Perrone AM, Kurelac I, et al (2012). Mitochondrial DNA mutation in serous ovarian cancer: implications for mitochondria-coded genes in chemoresistance. J Clin Oncol, 30, e373-8. https://doi.org/10.1200/JCO.2012.43.5933
  8. Guo W, Yang D, Xu H, et al (2013). Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma. Mol Boil Rep, 40, 13-20. https://doi.org/10.1007/s11033-012-1939-7
  9. Isidoro A, Martinez M, Fernandez PL, et al (2004). Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J, 378, 17-20. https://doi.org/10.1042/BJ20031541
  10. Jeong CW, Lee JH, Sohn SS, Ryu SW, Kim DK (2010). Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion. Cancer Epidemiol, 34, 323-7. https://doi.org/10.1016/j.canep.2010.03.015
  11. Lee HC, Li SH, Lin JC, et al (2004). Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat Res, 547, 71-8. https://doi.org/10.1016/j.mrfmmm.2003.12.011
  12. Lievre A, Chapusot C, Bouvier AM, et al (2005). Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol, 23, 3517-25. https://doi.org/10.1200/JCO.2005.07.044
  13. Lightowlers RN, Chinnery PF, Turnbull DM, Howell N (1997). Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet, 13, 450-5. https://doi.org/10.1016/S0168-9525(97)01266-3
  14. Lin CS, Lee HT, Lee SY, et al (2012). High mitochondrial DNA copy number and bioenergetic function are associated with tumor invasion of esophageal squamous cell carcinoma cell lines. Int J Mol Sci, 13, 11228-46. https://doi.org/10.3390/ijms130911228
  15. Lin CS, Wang LS, Chang SC, et al (2012). Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma. Oncol Rep, 28, 69-76.
  16. Mambo E, Gao X, Cohen Y, et al (2003). Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations. Proc Natl Acad Sci U S A, 100, 1838-43. https://doi.org/10.1073/pnas.0437910100
  17. Mambo E, Chatterjee A, Xing M, et al (2005). Tumor-specific changes in mtDNA content in human cancer. Int J Cancer, 116, 920-4. https://doi.org/10.1002/ijc.21110
  18. Masuyama M, Iida R, Takatsuka H, Yasuda T, Matsuki T (2005). Quantitative change in mitochondrial DNA content in various mouse tissues during aging. Biochim Biophys Acta, 1723, 302-8. https://doi.org/10.1016/j.bbagen.2005.03.001
  19. Matsuyama W, Nakagawa M, Wakimoto J, et al (2003). Mitochondrial DNA mutation correlates with stage progression and prognosis in non-small cell lung cancer. Hum Mutat, 21, 441-3. https://doi.org/10.1002/humu.10196
  20. Maximo V, Soares P, Seruca R, et al(2001). Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma. Genes Chromosom Cancer, 32, 136-43. https://doi.org/10.1002/gcc.1175
  21. Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P (2003). Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCRbased assay: lack of change of copy number with age.Nucleic Acids Res, 31, e61. https://doi.org/10.1093/nar/gng060
  22. Modica-Napolitano JS, Singh KK (2004). Mitochondrial dysfunction in cancer. Mitochondrion, 4, 755-62. https://doi.org/10.1016/j.mito.2004.07.027
  23. Peng Z, Xie C, Wan Q, et al (2011). Sequence variations of mitochondrial DNA D-loop region are associated with familial nasopharyngeal carcinoma. Mitochondrion, 11, 327-33. https://doi.org/10.1016/j.mito.2010.12.008
  24. Penta JS, Johnson FM, Wachsman JT, Copeland WC (2001). Mitochondrial DNA in human malignancy. Mutat Res, 488, 119-33. https://doi.org/10.1016/S1383-5742(01)00053-9
  25. Purdue MP, Hofmann JN, Colt JS, et al (2012). A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PloS One, 7, e43149. https://doi.org/10.1371/journal.pone.0043149
  26. Shidara Y, Yamagata K, Kanamori T, et al (2005). Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res, 65, 1655-63. https://doi.org/10.1158/0008-5472.CAN-04-2012
  27. Simonnet H, Alazard N, Pfeiffer K, et al (2002). Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis, 23, 759-68. https://doi.org/10.1093/carcin/23.5.759
  28. Sun YL, Fu L (2006). [Mutation of mitochondrial DNA in breast carcinoma]. Zhonghua Bing Li Xue Za Zhi, 35, 625-7.
  29. Tan W, Zhou W, Yu HG, Luo HS, Shen L (2013). The DNA methyltransferase inhibitor zebularine induces mitochondriamediated apoptosis in gastric cancer cells in vitro and in vivo. Biochem Biophys Res Commun, 430, 250-5. https://doi.org/10.1016/j.bbrc.2012.10.143
  30. Tseng LM, Yin PH, Chi CW, et al (2006). Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer, 45, 629-38. https://doi.org/10.1002/gcc.20326
  31. Wang L, Bamlet WR, de Andrade M, et al (2007). Mitochondrial genetic polymorphisms and pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev, 16, 1455-9. https://doi.org/10.1158/1055-9965.EPI-07-0119
  32. Wang S, Shen ZL (2012). [Considerations on the therapy of colorectal cancer liver metastasis in China]. Zhonghua Wei Chang Wai Ke Za Zhi, 15, 993-6.
  33. Wang Y, Liu VW, Tsang PC, et al (2006). Microsatellite instability in mitochondrial genome of common female cancers. Int J Gynecol Cancer, 16, 259-66. https://doi.org/10.1111/j.1525-1438.2006.00412.x
  34. Warburg O (1956). On the origin of cancer cells. Science, 123, 309-14. https://doi.org/10.1126/science.123.3191.309
  35. Xing J, Chen M, Wood CG, et al (2008). Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst, 100, 1104-12. https://doi.org/10.1093/jnci/djn213
  36. Yamada S, Nomoto S, Fujii T, et al (2006). Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma. Eur J Surg Oncol, 32, 303-7. https://doi.org/10.1016/j.ejso.2006.01.002
  37. Yin PH, Lee HC, Chau GY, et al (2004). Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer, 90, 2390-6.

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  3. The 9-bp deletion at position 8272 in region V of mitochondrial DNA is associated with renal cell carcinoma outcome pp.1940-1744, 2014, https://doi.org/10.3109/19401736.2014.971312
  4. Nuclear and mitochondrial DNAs microsatellite instability and mitochondrial DNA copy number in adenocarcinoma and squamous cell carcinoma of lung: a pilot study vol.123, pp.12, 2015, https://doi.org/10.1111/apm.12471
  5. Is Mitochondrial DNA Copy Number Associated with Clinical Characteristics and Prognosis in Gastric Cancer? vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.87
  6. Analysis of mitochondrial DNA alteration in new phenotype ACOS vol.16, pp.1, 2016, https://doi.org/10.1186/s12890-016-0192-6
  7. Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer vol.117, pp.2, 2017, https://doi.org/10.1038/bjc.2017.155