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High Frequency of Promoter Hypermethylation of RASSF1A in Nasopharyngeal Carcinoma

Departments of Anatomical and Cellular Pathology [K-W. L., J. K., A. B-Y. H., S. Y-Y. C., K-F. T., L. S-N. C., D. P. H.] and Clinical Oncology [P. M. L. T., P. J. J.], Prince of Wales Hospital, and Institute of Molecular Oncology at the Sir Y. K. Pao Centre for Cancer [K-W. L., A. S-C. C., P. M. L. T., P. J. J., D. P. H.], The Chinese University of Hong Kong, Hong Kong SAR, China

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. Promoter 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 were found in 2 of 21 (9.5%) primary tumors. In the cell lines and xenografts with extensive methylation, no RASSF1A gene expression was found. After treatment with 5'-aza-2'deoxycytidine, reexpression and demethylation of the RASSF1A gene were detected in a NPC cell line. These findings suggest that promoter hypermethylation may participate in the transcriptional inactivation of the RASSF1A gene in NPC. The high incidence of RASSF1A alterations suggest that it is the critical target gene on chromosome 3p21.3 involved in the development of NPC.

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