scholarly journals Proliferation Rates of Multiple Endocrine Neoplasia Type 1 (MEN1)-Associated Tumors

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5167-5179 ◽  
Author(s):  
Gerard V. Walls ◽  
Anita A.C. Reed ◽  
Jeshmi Jeyabalan ◽  
Mahsa Javid ◽  
Nathan R. Hill ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Second Order ◽  
Proliferating Cells ◽  
Autosomal Dominant Disorder ◽  
Adrenocortical Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Associated Tumors

Abstract Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid and adrenocortical tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. The pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary NETs are mostly prolactinomas and somatotrophinomas. We postulated that the different types of pancreatic and pituitary NETs may be partly due to differences in their proliferation rates, and we therefore assessed these in MEN1-associated tumors and gonadal tumors that developed in mice deleted for an Men1 allele (Men1+/−). To label proliferating cells in vivo, Men1+/− and wild-type (Men1+/+) mice were given 5-bromo-2-deoxyuridine (BrdU) in drinking water from 1–12 wk, and tissue sections were immunostained using anti-BrdU and hormone-specific antibodies. Proliferation in the tumors of Men1+/− mice was significantly (P < 0.001) increased when compared with the corresponding normal Men1+/+ tissues. Pancreatic, pituitary and adrenocortical proliferation fitted first- and second-order regression lines in Men1+/+ tissues and Men1+/− tumors, respectively, R2 = 0.999. Apoptosis was similar in Men1+/− pancreatic, pituitary, and parathyroid tumors when compared with corresponding normal tissues, decreased in Men1+/− adrenocortical tumors, but increased in Men1+/− gonadal tumors. Mathematical modeling of NET growth rates (proliferation minus apoptosis rates) predicted that in Men1+/− mice, only pancreatic β-cells, pituitary lactotrophs and somatotrophs could develop into tumors within a murine lifespan. Thus, our studies demonstrate that Men1+/− tumors have low proliferation rates (<2%), second-order kinetics, and the higher occurrence of insulinomas, prolactinomas, and somatotrophinomas in MEN1 is consistent with a mathematical model for NET proliferation.

scholarly journals Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (CDC73) Variant

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Kate E Lines ◽  
Lisa B Nachtigall ◽  
Laura E Dichtel ◽  
Treena Cranston ◽  
Hannah Boon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Endocrine Neoplasia ◽  
Kinase Inhibitor ◽  
Multiple Endocrine Neoplasia Type ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Autosomal Dominant Disorder ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Abstract Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid tumors, pituitary adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by germline MEN1 mutations in > 75% of patients, and the remaining 25% of patients may have mutations in unidentified genes or represent phenocopies with mutations in genes such as cell cycle division 73 (CDC73), the calcium sensing receptor (CASR), and cyclin-dependent kinase inhibitor 1B (CDKN1B), which are associated with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous c.1138C>T (p.Leu380Phe) CDC73 germline variant in a clinically diagnosed MEN1 patient, based on combined occurrence of primary hyperparathyroidism, acromegaly, and a PNEN. Characterization of the PNEN confirmed it was a neuroendocrine neoplasm as it immuno-stained positively for chromogranin and glucagon. The rare variant p.Leu380Phe occurred in a highly conserved residue, and further analysis using RNA-Scope indicated that it was associated with a significant reduction in CDC73 expression in the PNEN. Previously, CDC73 mutations have been reported to be associated with tumors of the parathyroids, kidneys, uterus, and exocrine pancreas. Thus, our report of a patient with PNEN and somatotrophinoma who had a CDC73 variant, provides further evidence that CDC73 variants may result in a MEN1 phenocopy.

scholarly journals Multiple endocrine neoplasia type 1 gene expression is normal in sporadic adrenocortical tumors

2000 ◽  
pp. 689-695 ◽  
Author(s):  
O Zwermann ◽  
F Beuschlein ◽  
P Mora ◽  
G Weber ◽  
B Allolio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Adrenocortical Tumors ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Adrenocortical Carcinomas

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with neoplasia of the anterior pituitary, the parathyroid, the endocrine pancreas and other endocrine tissues including the adrenal cortex. The tumor-suppressor gene causing this disease was identified at the gene locus 11q13. We recently reported that adrenocortical carcinomas frequently show loss of heterozygosity (LOH) of 11q13, but do not contain point mutations within the MEN1-coding region. To investigate whether reduced gene expression (for example by mutations within the MEN1 promoter) may contribute to the tumorigenesis of sporadic adrenocortical tumors, 24 adrenocortical specimen were studied by Northern blot analysis. This series included six adrenocortical carcinomas, four cortisol-producing adenomas, six aldosterone-producing adenomas, three endocrine-inactive adenomas and six normal adrenal glands. The presence of LOH of 11q13 was investigated using five polymorphic microsatellite markers (D11S956, PYGM, D11S4939, D11S4946 and D11S987) close to the MEN1 gene. Poly-A mRNA was hybridized with a PCR-generated cDNA probe of the MEN1 gene, a cDNA of the former MEN1 candidate gene phospholipase (PLC) beta3 and a mouse beta-actin cDNA for normalization. LOH of 11q13 was detected in five out of six carcinomas and two inactive adenomas, but in none of the hormone-producing adenomas. Compared with normal adrenals (100+/-6. 5%, mean+/-s.e.m.) MEN1 mRNA in adrenocortical tumors was expressed in similar amounts (carcinomas 109+/-11%, cortisol-producing adenomas 131+/-10%, aldosterone-producing adenomas 113+/-13%, endocrine-inactive adenomas 111+/-2%) with the exception of one adrenocortical carcinoma with low MEN1 mRNA expression (66%). PLCbeta3 mRNA expression showed a variable pattern without reaching significant differences between the groups. We conclude that since mRNA levels were unaltered in the majority of tumors, mutations of the MEN1 gene causing altered gene transcription is unlikely to be a major pathogenic factor of sporadic adrenocortical tumors.

scholarly journals Minimal Change Disease in a Patient with Multiple Endocrine Neoplasia Type 1

2020 ◽  
Vol 95 (5) ◽  
pp. 340-343
Author(s):  
Yunjung Ko ◽  
Mi Sun Ahn ◽  
Hyun Ee Yim ◽  
Min-Jeong Lee ◽  
Gyu-Tae Shin ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Minimal Change Disease ◽  
Multiple Endocrine Neoplasia Type ◽  
Relevant Literature ◽  
Minimal Change ◽  
Autosomal Dominant Disorder ◽  
Men 1 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by two or more tumors of the parathyroid gland, duodenum-pancreas, and anterior pituitary. Membranous nephropathy is the most common manifestation of paraneoplastic glomerulopathy. However, minimal change disease in patients with MEN 1 has yet to be reported. Here, we report a case of minimal change disease in a 59-year-old man with MEN 1, along with a review of the relevant literature.

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