A newly recognized germline mutation of MEN1 gene identified in a patient with parathyroid adenoma and carcinoma
ABSTRACT We report on a patient with primary hyperparathyroidism, owing to the concurrence of parathyroid adenoma with carcinoma, who
had a newly recognized germline mutation of the multiple endocrine neoplasia type 1 gene (MEN1 gene). The patient underwent total parathyroidectomy, and histological examination revealed parathyroid carcinoma and multiple
adenoma of the other three glands. Genetic analysis revealed a newly recognized heterozygous germline mutation (842deIC, exon
4) of the MEN1 gene. Both imaging studies and laboratory data showed no evidence of MEN 1 in the patient. Four family members—three sisters
and one daughter—had neither clinical features of MEN 1 nor genetic evidence of the MEN1 gene. This is the first report of a germline mutation of the MEN 1 gene found in a patient who exhibited the concurrence of parathyroid adenoma with carcinoma, suggesting that long-term hyperactivity
of the parathyroids may result in the formation of carcinoma.
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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.Expert Opinion on Medical Diagnostics 11/2007; 1(3):377-392.
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ABSTRACT: Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.The Cancer Journal 07/2012; 18(4):364-71. · 3.66 Impact Factor