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p16 INK4a is a tumor suppressor protein. It is a specific inhibitor of Cdk 4 / Cdk 6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. Recent analyses of the p16 INK4a gene revealed homozygous deletions, nonsense, missense, or frameshift mutations in several human cancers. Although the frequency of p16 INK4a abnormalities is higher in tumor derived cell lines than in unselected primary tumors, significant subsets of clinical cases with aberrant p16 INK4a gene have been reported among melanomas, gliomas, esophageal, pancreatic, lung, and urinary bladder carcinomas, and some types of leukemia.