title: Mutational analysis of CDKN1B, a candidate tumor-suppressor gene, in refractory secondary/tertiary hyperparathyroidism.
abstract: Most patients with refractory secondary/tertiary hyperparathyroidism have monoclonal parathyroid tumors. Inactivating mutations of CDKN1B, encoding the p27 cyclin-dependent kinase inhibitor, were reported to cause hyperparathyroidism in a multiple endocrine neoplasia type 1-like syndrome. Further, there was decreased expression of CDKN1B in parathyroid tumors of patients with chronic kidney disease. We sequenced the entire coding region and splice sites of CDKN1B in 50 parathyroid tumors from 35 patients to see if inactivating mutations could cause monoclonal tumorigenesis in refractory secondary/tertiary hyperparathyroidism. No frameshift, nonsense, or other clearly inactivating mutations were found, nor was there evidence of homozygous deletion or loss of heterozygosity. The absence of clonal inactivating mutations suggests that CDKN1B is not a classical tumor-suppressor gene in secondary/tertiary parathyroid tumors.
authors.affiliation: Center for Molecular Medicine, Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Lauter
authors.forename: A
authors.initials: A
authors.lastname: Arnold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004252:DNA Mutational Analysis; D016147:Genes, Tumor Suppressor; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000150:complications / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27