Parathyroid tumors are rare endocrine neoplasms affecting 0.1-0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2-1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.
Keywords: epigenetic signatures; gene mutations; parathyroid adenomas; parathyroid carcinomas; parathyroid tumors.