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Promoter Hypermethylation of Multiple Genes in Nasopharyngeal Carcinoma¹

Departments of Anatomical and Cellular Pathology [J. K., K-W. L., K-F. T., 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., P. J. J., D. P. H.], The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China

Purpose: The methylation profile of nasopharyngeal carcinoma (NPC) has been investigated by a candidate gene approach.

Experimental Design: Four NPC cell lines, 4 NPC xenografts, 33 NPC primary tumors, and 6 samples of normal nasopharyngeal epithelium were subjected to methylation-specific PCR for analysis of promoter methylation of eight cancer-related genes. These eight genes were RASSF1A, RARß2, DAP-kinase, p16, p15, p14, MGMT, and GSTP1. The correlation between methylation status of these genes and clinical features such as stage, local-regional recurrence, distant metastasis, and survival has been analyzed.

Results: The incidence of promoter methylation in NPC samples was 84% for RASSF1A, 80% for RARß2, 76% for DAP-kinase, 46% for p16, 17% for p15, 20% for p14, 20% for MGMT, and 3% for GSTP1. No methylation of these genes was detected in the six normal nasopharyngeal epithelium samples. All NPC tumor samples in this study displayed aberrant methylation in at least one of these eight genes. No significant correlation between methylation status of these genes and clinical parameters of the patients was found.

Conclusions: A high frequency of aberrant methylation of the 5' CpG island of the RASSF1A, RARß2, DAP-kinase, and p16 genes in the present study was noted. Our findings suggest that methylation of the genes in the critical pathways is common in NPC.

Key Article

The Potential Prognostic, Predictive, and Therapeutic Values of DNA Methylation in Cancer : Commentary re: J. Kwong et al., Promoter Hypermethylation of Multiple Genes in Nasopharyngeal Carcinoma. Clin. Cancer Res., 8: 131–137, 2002, and H-Z. Zou et al., Detection of Aberrant p16 Methylation in the Serum of Colorectal Cancer Patients. Clin. Cancer Res., 8: 188–191, 2002.

Martin Widschwendter and Peter A. Jones
Clin. Cancer Res. 2002 8: 17-21. [Full Text] [PDF]

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