Mitochondrial D-Loop Polymorphism and Microsatellite Instability in Prostate Cancer and Benign Hyperplasia Patients

  • Ashtiani, Zahra Ousati (Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences) ;
  • Heidari, Mansour (Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences) ;
  • Hasheminasab, Sayed-Mohammad (Department of Clinical Pharmacology, University Medical Center Gottingen (UMG)) ;
  • Ayati, Mohsen (Department of Urology, Imam Khomeini General Hospital, Tehran University of Medical Sciences) ;
  • Rakhshani, Naser (Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences)
  • Published : 2012.08.31


In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A${\rightarrow}$G and 310T${\rightarrow}$C among both BPH and prostate cancer patients. Variation of 309 C${\rightarrow}$T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G${\rightarrow}$A, np389G${\rightarrow}$A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C${\rightarrow}$T variation in cancer patients is a notable finding and must be a focus of attention in future studies.


  1. Ashtiani ZO, Hasheminasab SM, Ayati M, et al (2011). Are GSTM1, GSTT1 and CAG repeat length of androgen receptor gene polymorphisms associated with risk of prostate cancer in Iranian patients? Pathol Oncol Res, 17, 269-75.
  2. Booker L M, Habermacher G M, Jessie B C, et al (2006). North American white mitochondrial haplogroups in prostate and renal cancer. J Urol, 175, 468-72; discussion 472-3.
  3. Chatterjee A, Mambo E, Sidransky D (2006). Mitochondrial DNA mutations in human cancer. Oncogene, 25, 4663-74.
  4. Chen J Z, Gokden N, Greene G F, et al (2002). Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection. Cancer Res, 62, 6470-4.
  5. Copeland WC, Wachsman JT, Johnson FM, et al (2002). Mitochondrial DNA alterations in cancer. Cancer Invest, 20, 557-69.
  6. Czarnecka a M, Klemba A, Semczuk A, et al (2009). Common mitochondrial polymorphisms as risk factor for endometrial cancer. Int Arch Med, 2, 33.
  7. Fliss M S, Usadel H, Caballero O L, et al (2000). Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science, 287, 2017-9.
  8. Ghafouri-Fard S, Ousati Ashtiani Z, Sabah Golian B, et al (2010). Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer. Arch Med Res, 41, 195-200.
  9. Gomez-Zaera M, Abril J, Gonzalez L, et al (2006). Identification of somatic and germline mitochondrial DNA sequence variants in prostate cancer patients. Mutat Res, 595, 42-51.
  10. Guo XG, Guo QN (2006). Mutations in the mitochondrial DNA D-Loop region occur frequently in human osteosarcoma. Cancer Lett, 239, 151-5.
  11. Jeronimo C, Nomoto S, Caballero O L, et al (2001). Mitochondrial mutations in early stage prostate cancer and bodily fluids. Oncogene, 20, 5195-8.
  12. Kirches E, Krause G, Warich-Kirches M, et al (2001). High frequency of mitochondrial DNA mutations in glioblastoma multiforme identified by direct sequence comparison to blood samples. Int J Cancer, 93, 534-8.
  13. Lee HC, Yin PH, Lin JC, et al (2005). Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci, 1042, 109-22.
  14. Lievre A, Chapusot C, Bouvier a-M, et al (2005). Clinical value of mitochondrial mutations in colorectal cancer. J Clin Oncol, 23, 3517-25.
  15. Liu VWS, Yang HJ, Wang Y, et al (2003). High frequency of mitochondrial genome instability in human endometrial carcinomas. Br J Cancer, 89, 697-701.
  16. Lu J, Sharma LK, Bai Y (2009) Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res, 19, 802-15.
  17. Mueller E E, Eder W, Mayr J A, et al (2009). Mitochondrial haplogroups and control region polymorphisms are not associated with prostate cancer in Middle European Caucasians. PLoS One, 4, e6370.
  18. Ousati Ashtiani Z, Ayati M, Modarresi M H, et al (2009). Association of TGIFLX/Y mRNA expression with prostate cancer. Med Oncol, 26, 73-7.
  19. Pang LJ, Shao JY, Liang XM, et al (2008). Mitochondrial DNA somatic mutations are frequent in nasopharyngeal carcinoma. Cancer Biol Ther, 7, 198-207.
  20. Parkin DM, Bray FI, Devesa SS (2001). Cancer burden in the year 2000. The global picture. Eur J Cancer, 37, 4-66.
  21. Penta JS, Johnson FM, Wachsman JT, et al (2001). Mitochondrial DNA in human malignancy. Mutat Res, 488, 119-33.
  22. Petros J A, Baumann a K, Ruiz-Pesini E, et al (2005). mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA, 102, 719-24.
  23. Roylance R, Spurr N, Sheer D (1997) The genetic analysis of prostate carcinoma. Semin Cancer Biol, 8, 37-44.
  24. Sharawat SK, Bakhshi R, Vishnubhatla S, et al (2010). Mitochondrial D-loop variations in paediatric acute myeloid leukaemia: a potential prognostic marker. Br J Haematol, 149, 391-8.
  25. Shen L, Wei J, Chen T, et al (2011). Evaluating mitochondrial DNA in patients with breast cancer and benign breast disease. J Cancer Res Clin Oncol, 137, 669-75.
  26. Wallace DC (2005). A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet, 39, 359-407.
  27. Wang X (2001). The expanding role of mitochondria in apoptosis. Genes Dev, 15, 2922-33.

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