Wafa Troudi
Besma Loueslati
Amal Baccar
Farhat Ben Ayed
Amel Ben Ammar El Gaaied


Aim : The aim of this study is to evaluate the implication of BRCA1 gene and the mitochondrial micro satellite (situated between 303 and 315 positions) mutations in the occurrence of breast cancer in Tunisia.
Methods : Nine Tunisian patients with hereditary breast cancer have been analyzed. For each patient, total genomic DNA was extracted and used as a template for the amplification of 24 exons of the BRCA1 gene and an hyper variable mitochondrial region. The obtained products were purified and automatically sequenced.
Results : The results revealed five types of mutations for the micro satellite situated between the 303 and 315 positions and two deleterious BRCA1 mutations for two unrelated patients which present the same mitochondrial mutation (315.insC) suggesting his implication in the modulation of the BRCA1 deleterious mutations


Breast cancer, BRCA1 gene, mitochondrial DNA, Tunisia



  1. Hsairi M, Fakhfakh R, Ben Abdallah M, Jlidi R, Sellami A, Zheni S et al. Estimation à l'échelle nationale de l'incidence des cancers en Tunisie. 1993-1997. Tunisie Médicale 2002; 80: 57-64.
  2. Ben ahmed S, Aloulou S, Bibi M, Landolsi A, Nouira M, Ben Fatma L et al. Pronostic du cancer du sein chez les femmes tunisiennes. Analyse d'une série hospitalière de 729 patientes. Santé Publique 2002; 14: 231-41.
  3. Ferlay J, Boyle P. Cancer incidence, mortality and prevalence world wide. International Agency for Research on Cancer, Lyon, France 2004. Annals of Oncology 2005; 16: 481-488.
  4. Maalej M, Hentati D, Messai T, Kochbati L, El May A, Mrad K, Romdhane KB, Ben Abdallah M, Zouari B. Breast cancer in Tunisia in 2004: a comparative clinical and epidemiological study. Bull Cancer 2008; 95: 5-9.
  5. Hsairi M, Fakhfakh R, Bellaaj R, Achour N. Knowledge, attitudes and behaviors of women towards breast cancer screening. East Mediterr Health J 2003; 9:87-98.
  6. Ford D, Easton DF. The genetics of breast and ovarian cancer. Br J Cancer 1995; 72: 805-12.
  7. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999; 91: 943-9.
  8. Wooster R, Weber BL. Breast and ovarian cancer. N Engl J Med 2003; 348: 2339-47.
  9. Troudi W, Uhrhammer N, Sibille C, Dahan C, Mahfoudh W, Bouchlaka Souissi C et al. Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia. J Hum Genet 2007; 52: 915-920.
  10. Wang T, Lerer I, Gueta Z, Sagi M, Kadouri L, Peretz T, Abeliovich D. A deletion/insertion mutation in the BRCA2 gene in a breast cancer family: a possible role of the Alu-polyA tail in the evolution of the deletion. Genes Chromosomes Cancer 2001; 31: 91-5.
  11. Alonso A, Martin P, Albarran C, Aquilera B, Garcia O, Guzman A, Oliva H, Sancho M. Detection of somatic mutations in the mitochondrial DNA control region of colorectal and gastric tumors by heteroduplex and single-strand conformation analysis. Electrophoresis 1997; 18: 682-685.
  12. Zhu W, Qin W, Bradley P, Wessel A, Puckett CL, Sauter ER. Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis 2005; 26: 145-152.
  13. Parella P, Seripa D, Matera MG, Rabitti C, Rinaldi M, Mazzarelli P, Gravina C et al. Mutation of the D310 mitochndrial mononucleotide repeat in primary tumors cytological specimens.Cancer Letters 2003; 190: 147-150.
  14. Arena JF, Smith S, Plewinska M. BRCA1 mutations in African American women. Am J Hum Genet 1996; 59: Suppl A34.
  15. Frigi S, Yacoubi B, Pereira F, Pereira L, Amorim A, Elgaaied A. mtDNA lineages in two Tunisian Berber communities: comparing diversities between villages and towns. International Congress Series 2006; 1288: 121-123.
  16. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 1999; 23: 147.
  17. Sharma H, Singh A, Sharma C, Jain S K, Singh N. Mutations in the mitochondrial D-loop region are frequent in cervical cancer. Cancer Cell International 2005; 34: 1-6.
  18. Kang D, Miyako K, Kai Y, Irie T, Takeshige K. In vivo determination of replication origins of human mitochondrial DNA by ligation-mediated polymerase chain reaction. J Biol Chem 1997; 272: 15275-15279.
  19. Lee DY and Clayton DA. Initiation of mitochondrial DNA replication by transcription and R-loop processing. J Biol Chem 1998; 273: 30614-30621.