Inactivation of the p16 tumor suppressor gene in adrenocortical tumors

The mechanisms of adrenocortical tumorigenesis are still unknown. Evidence that the majority of adrenocortical tumors are monoclonal in origin suggest s that a progressive accumulation of genetic aberrations, due to activation of protooncogenes and/or inactivation of tumor suppressor genes, leads to abnormal cell proliferation through a multistep process. Inactivation of th e p16 tumor suppressor gene (p16(INK4A)), which encodes the cell cycle prot ein p16, was investigated in a series of 14 adrenocortical tumors. Using 11 polymorphic microsatellite markers spanning the short arm of chromosome 9, we demonstrated that three of seven adrenocortical carcinomas and one of s even adrenocortical adenomas had loss of heterozygosity (LOH) within chromo some 9p21, the region containing p16(INK4A). Immunohistochemistry showed th e absence of p16 nuclear staining in all adrenocortical tumors with LOH wit hin 9p21, and positive staining in all remaining tumors without LOH. In con clusion, LOH within 9p21 associated with lack of p16 expression occurs in a considerable proportion of adrenocortical malignant tumors, but is rare in adenomas. Inactivation of p16(INK4A) may contribute to the deregulation of cell proliferation in this neoplastic disease.