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Ataxia-Telangiectasia-Mutated (ATM) Gene in Head and Neck Squamous Cell Carcinoma

Promoter Hypermethylation with Clinical Correlation in 100 Cases

¹ Departments of Pathology and ² Otolaryngology, University of Arkansas for Medical Sciences and John L. McClellan Memorial Veterans’ Hospital, Little Rock, Arkansas; ³ College of Public Health, Sun-Yat Sen University, Guangzhou, People’s Republic of China; and ⁴ Department of Biochemistry and Molecular Biology and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana

The Ataxia-telangiectasia-mutated (ATM) gene product is a well-characterized tumor suppressor that plays a key role in maintenance of genomic stability. We have recently documented that the ATM promoter is a target for epigenetic silencing in cultured tumor cells. Here we show that aberrant methylation of the ATM promoter occurs in a significant percentage (25%) of head and neck squamous cell carcinomas. The presence of methylated ATM promoter shows a statistically significant correlation with an earlier age of initial diagnosis and decreased overall survival, particularly in early-stage tumors. These findings indicate that ATM promoter hypermethylation occurs in head and neck squamous cell carcinoma, and this feature is a potentially useful prognostic marker in this tumor type.

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