DELETED IN ORAL CANCER-1 (DOC-1), A NOVEL ORAL TUMOR-SUPPRESSOR GENE

We have identified, isolated, and partially characterized doc-1, a nov el cDNA sequence whose activity is consistent with a suppressor of ham ster oral carcinogenesis. Doc-1 is an evolutionarily conserved gene ex hibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes. The full-length doc-1 cDNA encod es an 87 amino acid product that shows a significant homology to one o f the seven novel genes induced in mouse fibroblasts by TNF-alpha. Tra nsfection of the full-length doc-1 cDNA into malignant hamster oral ke ratinocytes alters the behavior of the recipients in terms of morpholo gy, growth rate, and anchorage-independent growth, suggesting reversio n of transformation phenotypes. We propose that doc-1 is a novel tumor suppressor gene in oral cancer development.