Regulation of Hypermethylated Genes in NPC

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the squamous epithelium. Numerous genetic aberrations have been detected in NPC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Inactivation of TSGs by epigenetic modification, in particular DNA methylation, has become an important mechanism in tumorigenesis. Our previous work indicated that DNA methyltransferase (DNMT) expression is elevated in NPC tumor when compared with adjacent non-tumor (Tsai et al., 2006) suggesting DNA hypermethylation may be critical in NPC pathogenesis. In cancer cells, aberrant DNA methylation in promoter region often correlates with the inactivation or silencing of the TSG; hence, gene target of DNMT may be considered as TSG candidate. We have used a promoter methylation array and MassArray EpiTYPER (Sequenom) to identify two potential differential hypermethylated genes in NPC. Characterization of these differential methylated genes not only elucidates the molecular pathogenesis of NPC, but also allows us to develop diagnostic tumor markers and therapeutic targets. Therefore, the aim of this proposal is (1) to validate methylation status of these two genes in NPC clinical samples and cell lines; (2) to examine the biological functions of these hypermethylated genes and their roles in NPC; (3) to test whether LMP1 can mediate hypermethylation of these two genes; and (4) to test whether the methylation degree of these two genes together with previously known TSGs can serve as early NPC prognostic biomarkers.

Project ID:PC9808-0569
External Project ID:NSC98-2320-B182-033-MY2