Hypermethylation of a Cluster of Kruppel-Type Zinc Finger Protein Genes on Chromosome 19q13 in Oropharyngeal Squamous Cell Carcinoma

Identification of epigenetically affected genes has become an important tool for understanding both normal and aberrant gene expression in cancer. Here we report a whole-genome analysis of DNA methylation profiles in fresh-frozen oropharyngeal squamous cell carcinoma (OPSCC) tissues and normal mucosa samples using microarray technology with patient genomic DNA. We initially compared whole-genome patterns of DNA methylation among 24 OPSCC primary tumors and 24 matched normal mucosal samples. From a survey of 27,578 CpG dinucleotide loci spanning more than 14,000 genes, we identified 958 CpG loci in which measurements of DNA methylation were altered in the primary tumors relative to the normal mucosal samples. These alterations were validated in an independent set of 21 OPSCC patients. A survey of these loci by chromosomal location revealed an abnormally high number of differentially methylated loci on chromosome 19. Many of the loci on chromosome 19 are associated with genes belonging to the Kruppel-type zinc finger protein genes. Hypermethylation was accompanied by a significant decrease in expression of these genes in OPSCC primary tumors relative to adjacent mucosa. This study reports the epigenetic silencing of Kruppel-type zinc finger protein genes on chromosome 19q13 in oropharyngeal cancer. The aberrant methylation of these genes represents a new avenue of exploration for pathways affected in this disease. (Am J Pathol 2011, 178:1965-1974; DOI: 10.1016/j.ajpath.2011.01.049)