Association study of LMP-1expression and promoter methylation status of tumor suppressor gene RASSF1A in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a cancer originating from nasopharyngeal epithelial tissue. Genetic susceptibility, exposure to carcinogens, and Epstein-Barr virus (EBV) infection are the main factors in NPC development. Latent membrane protein 1 (LMP-1) is a product of EBVgenome, which is able to interact with various intracellular signaling pathways that leads to expression of many proteins, e.g DNA methyltransferase. The increase expression of DNA methyltransferase could induce hypermetylation of tumor suppressor genes (TSG). Ras-association domain family 1A (RASSF1A) is one of TSG that frequently hypermethylated in NPC cases. The aim of this study is to determine the association between LMP-1 expression and promoter methylation status of RASSF1A in NPC patients. The research subjects were 36 NPC patients of the Dr. Sardjito Hospital, Yogyakarta, Indonesia. Latent membrane protein 1 was stained immunohistochemically using monoclonal antibody OT21 C. Ras-association domain family 1A methylation status was examined by methylation specific PCR (MSP) of DNA isolated from nasopharyngeal brushing. Chi-square analysis was conducted to examine the association between LMP-1 expression and methylation status of RASSF1A with 95% confidence interval. Latent membrane protein 1 was expressed in 44.4% subjects. The scores of ~MP-1 expression were ranged from 0-8 (average of 1.56 :t 2.16). Ras-association domain family 1A methylated in 66.7% of subjects. Statistical analysis showed that there was a relationship between LMP-1 expression and methylation status of RASSF1A (

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