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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...
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Published in: | Journal of cancer research and clinical oncology 2010-02, Vol.136 (2), p.203-210 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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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. |
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ISSN: | 0171-5216 1432-1335 |
DOI: | 10.1007/s00432-009-0649-6 |