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Inactivation of the p16 Tumor Suppressor Gene in Adrenocortical Tumors¹

Department of Medical and Surgical Sciences, Division of Endocrinology (C.P., M.P., A.M., U.P., M.B., F.F.), and the Department of Pathology (G.A.), University of Padova, 35128 Padova, Italy

Address all correspondence and requests for reprints to: Francesco Fallo, M.D., Department of Medical and Surgical Sciences, Division of Endocrinology, Via Ospedale 105, 35128 Padova, Italy.

The mechanisms of adrenocortical tumorigenesis are still unknown. Evidence that the majority of adrenocortical tumors are monoclonal in origin suggests 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 the p16 tumor suppressor gene (p16^INK4A), which encodes the cell cycle protein 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 seven adrenocortical adenomas had loss of heterozygosity (LOH) within chromosome 9p21, the region containing p16^INK4A. Immunohistochemistry showed the absence of p16 nuclear staining in all adrenocortical tumors with LOH within 9p21, and positive staining in all remaining tumors without LOH. In conclusion, 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.

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