title: Genetic and epigenetic changes in sporadic endocrine tumors: parathyroid tumors.
abstract: Parathyroid neoplasia is most commonly due to benign parathyroid adenoma but rarely can be caused by malignant parathyroid carcinoma. Evidence suggests that parathyroid carcinomas rarely, if ever, evolve through an identifiable benign intermediate, with the notable exception of carcinomas associated with the familial hyperparathyroidism-jaw tumor syndrome. Several genes have been directly implicated in the pathogenesis of typical sporadic parathyroid adenoma; somatic mutations in the MEN1 tumor suppressor gene are the most frequent finding, and alterations in the cyclin D1/PRAD1 oncogene are also firmly established molecular drivers of sporadic adenomas. In addition, good evidence supports mutation in the CDKN1B/p27 cyclin-dependent kinase inhibitor (CDKI) gene, and in other CDKI genes as contributing to disease pathogenesis in this context. Somatic defects in additional genes, including β-catenin, POT1 and EZH2 may contribute to parathyroid adenoma formation but, for most, their ability to drive parathyroid tumorigenesis remains to be demonstrated experimentally. Further, genetic predisposition to sporadic presentations of parathyroid adenoma appears be conferred by rare, and probably low-penetrance, germline variants in CDKI genes and, perhaps, in other genes such as CASR and AIP. The HRPT2 tumor suppressor gene is commonly mutated in parathyroid carcinoma.
authors.affiliation: Center for Molecular Medicine and Division of Endocrinology & Metabolism, University of Connecticut School of Medicine, Farmington, CT 06030-3101, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Costa-Guda
authors.affiliation: Center for Molecular Medicine and Division of Endocrinology & Metabolism, University of Connecticut School of Medicine, Farmington, CT 06030-3101, USA. Electronic address: molecularmedicine@uchc.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
mesh_terms: D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Hyperparathyroidism; Parathyroid adenoma; Parathyroid carcinoma
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