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 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 (p16INK4A), 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 p16NK4A. 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 p16INK4A may contribute to the deregulation of cell proliferation in this neoplastic disease.
Pilon
C
C
Department of Medical and Surgical Sciences, University of Padova, Italy.
Pistorello
M
M
Moscon
A
A
Altavilla
G
G
Pagotto
U
U
Boscaro
M
M
Fallo
F
F
D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D002899:Chromosomes, Human, Pair 9; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins