The Establishment Of Methylation Profile Of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is inclined to the epigenetic abnormal disease. Promoter CpG islands hypermethylation inactivated the expression of tumor suppress gene which caused the loosing of tumor suppress function played an important role in the NPC pathogenesis.To generate a global profile of genes silenced by hypermethylation in NPC cell, we analyzed genes reactivated in the NPC cell lines CNE2 and HONE1 after treatment with the 5-aza-dC and TSA by cDNA expression microarray-based. Choosing those genes with CpG islands from the up-regulated genes by 5-aza-dC, we primarily established the methylation profile of NPC.FSTL1, MAEL, TFPI2 and SPARC, randomly selected from the profile, were conformed repressed by semi-quantitative RT-PCR in NPC cell lines CNE2, HONE1 and C666-1 compared the expression with these cell lines after 5-aza-dC treatment. It validated that the 5-aza-dC can restore these genes in NPC cell lines.FSTL1, silenced in many kinds of tumors, was identified as a tumor suppress gene in ovarian and endometrial carcinogenesis. Expression of FSTL1 was down-regulated in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of FSTL1 could be observed in 100% (6/6) of the NPC cell lines and 68.6% (24/35) of primary tumors, but not in any of the normal epithelia. FSTL1 is frequently inactivated by its promoter methylation.