[Aberrant promoter hypermethylation of CHFR in nasopharyngeal carcinoma].

Objective: To discover the relationship of transcriptional levels and promoter methylation status of CHFR gene in human nasopharyngeal carcinoma,to discuss the significance and epigenetic mechanism of CHFR inactivation in NPC, and to evaluate the feasibility of detecting methylated CHFR in nasopharyngeal swab as a means for diagnosis of NPC.
Method: Transcriptional levels of CHFR was evaluated by RT-PCR. Methylation specific PCR was used to detect the methylation status of CHFR in NPC cells, normal nasopharyngeal epithelia, primary tumors and their paired nasopharyngeal swabs. Detailed methylation status was confirmed by bisulfite sequencing. NPC cells were treated by the methyltransferase inhibitor 5-aza-dC and the reactivation of CHFR was evaluated by RT-PCR.
Result: CHFR transcription was inactivated in NPC. The methylation frequency in NPC primary tumors and their paired swabs were 65.5% and 63.8%, respectively, with a 86.2% concordance. Bisulfite sequencing revealed a dense methylation in NPC cells and primary tumors, but all the normal nasopharyngeal epithelia were unmethylated. CHFR expression were restored after 5-aza-dC treatment.
Conclusion: CHFR is epigenetically inactivated by promoter methylation in NPC. Detecting methylated CHFR can be served as a useful non-invasive means for diagnosis of NPC.