Clinical significance of promoter hypermethylation of RASSF1A, RARβ2, BRCA1 and HOXA5 in breast cancers of Indian patients

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• 作者：Sarangadhara Appala Raju Bagadi ; Ch ; ra Prakash Prasad ; Jatinder Kaur ; Anurag Srivastava ; Rajinder Prashad ; Siddartha Datta Gupta ; Ranju Ralhan
• 关键词：Promoter hypermethylation ; RASSF1A ; RARβ ; 2 ; BRCA1 ; HOXA5 ; Breast cancer
• 刊名：Life Sciences
• 出版年：2008
• 出版时间：20 June 2008
• 年：2008
• 卷：82
• 期：25-26
• 页码：1288-1292
• 全文大小：326 K

文摘

Promoter hypermethylation of genes is implicated in the pathogenesis of many cancers, including breast cancer. Herein, we analyzed the promoter methylation status of a panel of critical growth regulatory genes, RASSF1A, RARβ2, BRCA1 and HOXA5, in 54 breast cancers and 5 distant normal breast tissues of Indian patients. The methylation data were correlated with clinicopathological characteristics and hormone receptor status to determine the impact of methylation in breast carcinogenesis. Promoter hypermethylation of RASSF1A was observed in 39/54 (72 % ), HOXA5 in 36/54 (67 % ), BRCA1 in 15/54 (28 % ) and RARβ2 in 8/54 (15 % ) breast cancers. Our most significant findings were the association of RASSF1A methylation with nodal metastasis (p = 0.05); and RARβ2 methylation with age (all tumors in patients in the older age group were methylated, p = 0.04). Further, the interactions between DNA methylation and hormone receptor biology in breast cancer cells are beginning to be clearly understood. In this context the association of HOXA5 methylation with loss of ER (p = 0.009) is noteworthy.