Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma.
In search for putative tumor suppressor genes critical of nasopharyngeal carcinoma (NPC), we analyzed the available information from the expression profiling in conjunction with the comprehensive alleotyping published data relevant to this malignancy. Integration of this information suggested eight potential candidate tumor suppressor genes, CCNA1, HRASLS3, RARRES1, CLMN, EML1, TSC22, LOH11CR2A and MCC. However, to confirm the above observations, we chose to investigate if promoter hypermethylation of these candidate genes would be one of the mechanisms responsible for the de-regulation of gene expression in NPC in addition to the loss of genetic materials. In this study, we detected consistent hypermethylation of the 5' element of CCNA1, RARRES1, and HRASLS in NPC tissues with prevalence of 48%, 51%, and 17%, respectively. Moreover, we found a similar profile of promoter hypermethylation in primary cultured NPC cells but none in normal nasopharyngeal epithelium or leukocytes, which further substantiate our hypothesis. Our data indicate that CCNA1, RARRES1, and HRASLS3 may be the putative tumor suppressor genes in NPC.
Yanatatsaneejit
Pattamawadee
P
Inter-Department of Biomedical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Chalermchai
Thep
T
Kerekhanjanarong
Veerachai
V
Shotelersuk
Kanjana
K
Supiyaphun
Pakpoom
P
Mutirangura
Apiwat
A
Sriuranpong
Virote
V
D019925:Cyclin A / Q000235:genetics; D056750:Cyclin A1; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D054512:Phospholipases A2, Calcium-Independent; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics
C503745:CCNA1 protein, human; D019925:Cyclin A; D056750:Cyclin A1; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C452562:RARRES1 protein, human; D025521:Tumor Suppressor Proteins; C490065:PLAAT3 protein, human; D054512:Phospholipases A2, Calcium-Independent