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Molecular Genetics of Parathyroid Disease

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Abstract

Background

Primary hyperparathyroidism (HPT) is often caused by a benign parathyroid tumor, adenoma; less commonly by multiglandular parathyroid disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple tumors require wider exploration to avoid recurrence and have increased risk for hereditary disease. Secondary HPT is a common complication of renal failure. Improved knowledge of the molecular background of parathyroid tumor development may help select patients for appropriate surgical treatment and can eventually provide new means of treatment. The present contribution summarizes more recent knowledge of parathyroid molecular genetics.

Methods

A literature search and review was made to evaluate the level of evidence concerning molecular biology and genetics of primary, secondary, and familial HPT according to criteria proposed by Sackett, with recommendation grading by Heinrich et al.

Results

Most parathyroid adenomas and hyperplastic glands are monoclonal lesions. Cyclin D1 gene (CCND1) translocation and oncogene action occur in 8% of adenomas; cyclin D1 overexpression is seen in 20% to 40% of parathyroid adenomas and in 31% of secondary hyperplastic glands. Somatic loss of one MEN1 allele is seen in 25% to 40% of sporadic parathyroid adenomas, half of which have inactivating mutation of the remaining allele. Inactivating somatic HRPT2 mutations are common in parathyroid carcinoma, often causing decreased expression of the protein parafibromin involved in cyclin D1 regulation. Aberrant regulation of Wnt/β-catenin signaling may be important for parathyroid tumor development.

Conclusions

Molecular genetic studies of parathyroid tumors are well designed basic experimental studies providing strong level III evidence, with data frequently confirmed by subsequent studies.

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  1. Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden

    Gunnar Westin, Peyman Björklund & Göran Åkerström

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  1. Gunnar Westin
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  2. Peyman Björklund
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Correspondence to Gunnar Westin.

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Westin, G., Björklund, P. & Åkerström, G. Molecular Genetics of Parathyroid Disease. World J Surg 33, 2224–2233 (2009). https://doi.org/10.1007/s00268-009-0022-6

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