Loading…

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

Introduction 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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2010-02, Vol.136 (2), p.203-210
Main Authors: Karray-Chouayekh, Sondes, Trifa, Fatma, Khabir, Abdelmajid, Boujelbane, Nouredine, Sellami-Boudawara, Tahia, Daoud, Jamel, Frikha, Mounir, Jlidi, Rachid, Gargouri, Ali, Mokdad-Gargouri, Raja
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Introduction 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. Results 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). Conclusions 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.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-009-0649-6