Molecular diagnosis of primary hyperparathyroidism in familial cancer syndromes
Deborah J Marsh1, Michael A Hahn, Viive M Howell
1University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia +61 2 9926 8486 ; +61 2 9926 8484 ; dmarsh@med.usyd.edu.au.
Abstract:
In the last few years, causative genes have been identified for most of the familial hyperparathyroidism conditions. Germline mutations in the tumour suppressors multiple endocrine neoplasia type 1 (MEN1) and hyperparathyroidism 2 (HRPT2) provide a molecular diagnosis of multiple endocrine neoplasia type 1 and hyperparathyroidism jaw tumour syndrome, respectively. Germline mutations in the proto-oncogene RET (rearranged during transfection) provide a molecular diagnosis of multiple endocrine neoplasia type 2. Germline mutations of both MEN1 and, less frequently HRPT2, have been found in familial isolated hyperparathyroidism. A molecular diagnosis can now be incorporated into the management of patients with these conditions, however, the ease of diagnostics and value of genetic information in the context of clinical screening and early surgical intervention varies between these disorders. This review focuses on familial hyperparathyroidism and its known causative genes in the setting of neoplastic syndromes, with particular discussion of recent developments in the molecular diagnosis of parathyroid carcinoma.
Insights
Genetic testing now diagnoses most familial hyperparathyroidism, including MEN1 and HRPT2. This review covers causative genes and molecular diagnostics for parathyroid carcinoma.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Familial hyperparathyroidism (FHP) is increasingly diagnosed through genetic testing.
- Key causative genes identified include MEN1, HRPT2, and RET, linked to specific endocrine neoplasia syndromes.
- Germline mutations in MEN1 and HRPT2 are also implicated in familial isolated hyperparathyroidism.
Purpose of the Study:
- To review the causative genes for familial hyperparathyroidism conditions.
- To discuss the role of molecular diagnostics in managing neoplastic syndromes associated with FHP.
- To highlight recent advancements in the molecular diagnosis of parathyroid carcinoma.
Main Methods:
- Literature review of causative genes for familial hyperparathyroidism.
- Analysis of molecular diagnostic approaches for MEN1, HRPT2, and RET mutations.
- Focus on genetic insights relevant to parathyroid carcinoma.
Main Results:
- Molecular diagnoses are available for most FHP conditions through identified germline mutations.
- The utility of genetic information varies across disorders for clinical screening and surgical intervention.
- Recent developments offer improved molecular diagnosis for parathyroid carcinoma.
Conclusions:
- Genetic testing provides a molecular diagnosis for major familial hyperparathyroidism syndromes.
- Integrating genetic information into clinical management requires tailored approaches based on the specific disorder.
- Advances in molecular diagnostics are crucial for early detection and management of parathyroid carcinoma.
