Abstract
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.
Highlights
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Yu et al [41] identified a germinal mutation associated with somatic loss of heterozygosity (LOH) at the gene locus on chromosome 9, two somatic missense mutations and two somatic nonsense mutations of the Prune Homolog 2 with BCH Domain (PRUNE2) gene, that all failed to be found in 40 sporadic parathyroid adenomas (PAs), revealing mutations of this gene as a recurrent event in carcinoma and as a possible distinctive genetic signature of sporadic parathyroid carcinomas (PCs)
Extremely rare cases of PCs have been associated with mutations of the Multiple Endocrine Neoplasia Type 1 (MEN1) tumor suppressor gene and the REarranged during Transfection (RET) proto-oncogene
Summary
The parathyroids are four small endocrine glands located in the neck behind the thyroid They are the “endocrine controllers” of calcium homeostasis that continuously monitor and regulate serum calcium levels through the synthesis and release of parathyroid hormone (PTH). Parathyroid tumors, and the related PHPT, manifest primarily as a sporadic singlegland disease in over 90% of cases, while only about 1 in 10 cases are hereditary familial forms, which can affect from 1 to 4 parathyroids [4] (Table 1). Inherited forms include both familial isolated parathyroid tumors and four autosomal dominant syndromic forms, in which the parathyroid neoplasms are associated with other endocrine and non-endocrine abnormalities.
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