High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma

We have investigated the genetic and epigenetic changes of a newly isolated tumor suppressor gene on 3p21.3, RASSF1A, in nasopharyngeal carcinoma (NPC ), Four xenografts, four cell lines and 21 primary tumors were examined. Pr omoter hypermethylation of the 5 ' CpG island of RASSF1A was detected in 4 of 4 (100%) xenografts, in 3 of 4 (75%) cell lines, and in 14 of 21 (66.7%) primary tumors but not in the normal nasopharyngeal epithelia. Mutations w ere found in 2 of 21 (9.5%) primary tumors. In the cell lines and xenograft s with extensive methylation, no RASSF1A gene expression was found, After t reatment with 5 ' -aza-2 ' -deoxycytidine, reexpression and demethylation o f the RASSF1A gene were detected in a NPC cell line. These findings suggest that promoter hypermethylation may participate in the transcriptional inac tivation of the RASSF1A gene in NPC, The high incidence of RASSF1A alterati ons suggest that it is the critical target gene on chromosome 3p21.3 involv ed in the development of NPC.