Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 2, pp 203–210 | Cite as

Aberrant methylation of RASSF1A is associated with poor survival in Tunisian breast cancer patients

  • Sondes Karray-Chouayekh
  • Fatma Trifa
  • Abdelmajid Khabir
  • Nouredine Boujelbane
  • Tahia Sellami-Boudawara
  • Jamel Daoud
  • Mounir Frikha
  • Rachid Jlidi
  • Ali Gargouri
  • Raja Mokdad-Gargouri
Original Paper



Epigenetic gene silencing is one of the major causes of inactivation of tumor-suppressor genes in many human cancers.

Materials and methods

The aim of the present study was to determine the methylation status of the promoter region CpG islands of four cancer-related genes RASSF1A, RARβ2, CDH1, and p16 INK4a in 78 breast cancer specimens and to evaluate whether the methylation status is associated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) together with the major clinico-pathological parameters.


We showed that the methylation frequencies ranged from 19.6% (p16 INK4a ) to 87% (RASSF1A) in primary breast tumors of Tunisian patients. Aberrant methylation of RARβ2 was observed in 66.6% of cases and associated with age at diagnosis (P = 0.043), while CDH1 was methylated in 47.4% of tumors and was correlated with tumor size (P = 0.013). RASSF1A presented the highest percentage of methylation (87%) and was strongly associated with poor survival (P = 0.014), with age (P = 0.048), and tumor stage (P = 0.033). Loss of ER and PR was strongly associated with GIII tumors (P = 0.000 and 0.037 respectively) while HER2/neu was associated with lymph node involvement (P = 0.026) and 5-year survival rate (P = 0.028).


Our preliminary findings suggested that aberrant methylation of RASSF1A and RARβ2 occurs frequently in Tunisian breast cancer patients compared with others. Furthermore, RASSF1A hypermethylation could be used as a potential marker of poor prognosis.


Promoter methylation Methylation-specific PCR Tumor suppressor genes Breast cancer Disease-free survival 



This work was supported by a grant of the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique Tunisien.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sondes Karray-Chouayekh
    • 1
  • Fatma Trifa
    • 1
  • Abdelmajid Khabir
    • 2
  • Nouredine Boujelbane
    • 2
  • Tahia Sellami-Boudawara
    • 2
  • Jamel Daoud
    • 2
  • Mounir Frikha
    • 2
  • Rachid Jlidi
    • 3
  • Ali Gargouri
    • 1
  • Raja Mokdad-Gargouri
    • 1
  1. 1.Unité de Recherche Génétique du Cancer et Production de Protéines ThérapeutiquesCentre de Biotechnologie de SfaxSfaxTunisia
  2. 2.Centre Hospitalo-Universitaire Habib BourguibaSfaxTunisia
  3. 3.Laboratoire privé d’Anatomo-pathologieSfaxTunisia

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