scholarly journals Multiple endocrine neoplasia type 1 knockout mice develop parathyroid, pancreatic, pituitary and adrenal tumours with hypercalcaemia, hypophosphataemia and hypercorticosteronaemia

2009 ◽  
Vol 16 (4) ◽  
pp. 1313-1327 ◽  
Author(s):  
Brian Harding ◽  
Manuel C Lemos ◽  
Anita A C Reed ◽  
Gerard V Walls ◽  
Jeshmi Jeyabalan ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Molecular Mechanisms ◽  
Multiple Endocrine Neoplasia Type ◽  
Somatostatin Receptor ◽  
Tumour Suppressor ◽  
Pituitary Tumours ◽  
Adrenal Tumours ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour suppressor. To investigate the in vivo role of menin, we developed a mouse model, by deleting Men1 exons 1 and 2 and investigated this for MEN1-associated tumours and serum abnormalities. Men1+/− mice were viable and fertile, and 220 Men1+/− and 94 Men1+/+ mice were studied between the ages of 3 and 21 months. Survival in Men1+/− mice was significantly lower than in Men1+/+ mice (<68% vs >85%, P<0.01). Men1+/− mice developed, by 9 months of age, parathyroid hyperplasia, pancreatic tumours which were mostly insulinomas, by 12 months of age, pituitary tumours which were mostly prolactinomas, and by 15 months parathyroid adenomas and adrenal cortical tumours. Loss of heterozygosity and menin expression was demonstrated in the tumours, consistent with a tumour suppressor role for the Men1 gene. Men1+/− mice with parathyroid neoplasms were hypercalcaemic and hypophosphataemic, with inappropriately normal serum parathyroid hormone concentrations. Pancreatic and pituitary tumours expressed chromogranin A (CgA), somatostatin receptor type 2 and vascular endothelial growth factor-A. Serum CgA concentrations in Men1+/− mice were not elevated. Adrenocortical tumours, which immunostained for 3-β-hydroxysteroid dehydrogenase, developed in seven Men1+/− mice, but resulted in hypercorticosteronaemia in one out of the four mice that were investigated. Thus, these Men1+/− mice are representative of MEN1 in man, and will help in investigating molecular mechanisms and treatments for endocrine tumours.

scholarly journals Clues For Genetic Anticipation In Multiple Endocrine Neoplasia Type 1

2020 ◽  
Vol 105 (7) ◽  
pp. e2491-e2500
Author(s):  
Medard F M van den Broek ◽  
Bernadette P M van Nesselrooij ◽  
Carolina R C Pieterman ◽  
Annemarie A Verrijn Stuart ◽  
Annenienke C van de Ven ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Multiple Endocrine Neoplasia ◽  
Molecular Mechanisms ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Anticipation ◽  
Screening Programs ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Successive Generations

Abstract Context Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by the loss of function of the MEN1 gene, a tumor-suppressor gene that encodes the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs. Objective To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands. Methods All Dutch MEN1 families with ≥ 10 affected members in ≥ 2 successive generations were identified. Age at detection of the different MEN1-related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for the beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared. Results A total of 152 MEN1 patients from 10 families were included. A significantly decreased age at detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations (P &lt; 0.0001). Adjusted analyses led to the same results. Conclusions These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future, more personalized, screening protocols and earlier screening for future generations of MEN1 patients.

Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types

1997 ◽  
Vol 47 (5) ◽  
pp. 507-512 ◽  
Author(s):  
Sabrina Corbetta ◽  
Alessandro Pizzocaro ◽  
Maddalena Peracchi ◽  
Paolo Beck-Peccoz ◽  
Giovanni Faglia ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Pituitary Tumours ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Different Types

scholarly journals Possible association between Carney complex and multiple endocrine neoplasia type 1 phenotypes

2008 ◽  
Vol 52 (8) ◽  
pp. 1356-1361 ◽  
Author(s):  
Vania S. Nunes ◽  
Cláudia V. Chang ◽  
Gláucia M. F. S. Mazeto ◽  
Mariângela E. A. Marques ◽  
Ana Valéria B. Castro ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Multiple Endocrine Neoplasia ◽  
Molecular Mechanisms ◽  
Multiple Endocrine Neoplasia Type ◽  
Carney Complex ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Affected Relative ◽  
Major Criterion

Carney Complex (CNC) and Multiple Endocrine Neoplasia type 1 (MEN1) are forms of multiple endocrine neoplasia of dominant autosomal inheritance. Diagnosis of CNC occurs when two major criteria (lentiginoses, primary pigmented nodular adrenocortical disease, cardiac and cutaneous myxomas, acromegaly, testicular neoplasias, thyroid cancer) are observed and/or a major criterion associated with a supplementary criterion (affected relative, PRKAR1A gene mutation) occurs. On the other hand, diagnosis for MEN1 occurs through detection of two or more tumors located at the pituitary gland, parathyroid and/or pancreatic cells. The present case describes a 55 year-old male patient, diagnosed with acromegaly, primary hyperparathyroidism and papillary thyroid cancer, exhibiting components that meet the diagnostic criteria of both conditions described. Despite the occurrence of only one sporadic association or the acromegaly per se being responsible for the papillary cancer, new molecular mechanisms may not be ruled out.

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