Thesis (Ph.D.)--Chulalongkorn University, 2007

To search for new candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC), we studied from the expression profiling compare between tumor and normal tissues. We selected 8 down regulated genes which can be divided into 2 groups, the first group is the genes which are tumor suppressor genes in other cancer, RARRES1' HRASLS3, LOH11CR2A and MCC. The other is the genes which are in the critical region of loss of heterozygosity(LOH); CCNA1, CLMN, EML1 and TSC22. Promoter hypermethylation, which is the major factor, leads to suppress gene expression. In this study, we detected promoter hypermethylation on promoter of the 8 candidate genes in NPC, normal leukocytes. Only 3 genes had promoter hypermethylation in NPC but not in normal leukocyte; CCNA1, RARRES1 and HRASLS3. We next increased the sample of NPC to around 100 cases, normal leukocyte 30 cases and normal epithelium cells 20 cases, there was promoter hypermethylation on CCNA1 57%, RARRES1 54% and HRASLS3 24%. Moreover, we could detect promoter hypermethylation onCCNA1 100%, RARRES1 83% and HRASLS3 17% in primary culture cells. This study, we concluded that CCNA1, RARRES1 and HRASLS3 might be act as new tumor suppressor genes in NPC