HYPERMETHYLATION OF THE P16 GENE IN NASOPHARYNGEAL CARCINOMA

We have recently reported that inactivation of the p16 gene by mutatio n and deletion is common in nasopharyngeal carcinoma (NPC). The presen t study demonstrates that hypermethylation of the 5' CpG island can se rve as an alternative mechanism for inactivation of the p16 gene in th is tumor, Using Southern blotting analysis and multiplex PCR, aberrant methylation of the 5' CpG island of the p16 gene was found in a NPC x enograft (xeno-666) and 6 (22%) of 27 primary tumors, but not in norma l tissues of the nasopharynx, In the NPC xenograft (xeno-666) and its newly derived cell line (cell-666), both showing hypermethylation of t he p16 gene, no p16 gene expression was found, After treatment with 5- aza-2'-deoxycytidine, reexpression of the p16 gene was detected in the cell line cell-666. These findings suggest that aberrant methylation of the 5' CpG island may participate in the transcriptional inactivati on of the pld gene in NPC, The present results further support that th e p16 gene is the critical target on chromosome 9p21 for inactivation during the development of this disease.