Disease relevance of Multiple Endocrine Neoplasia

• Cushing's syndrome due to ectopic ACTH secretion by bilateral pheochromocytomas in multiple endocrine neoplasia type 2A [1].
• Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2 [2].
• In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas [3].
• Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A) [4].
• The relevance was confirmed by showing elevated tissue and plasma PAI-2 in hypergastrinemic patients (pernicious anemia and multiple endocrine neoplasia type 1) [5].

High impact information on Multiple Endocrine Neoplasia

• Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown [6].
• Familial multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, endocrine pancreas, and anterior pituitary [7].
• We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause [8].
• Multiple endocrine adenomatosis type I. Occurrence in an octogenarian with high levels of circulating pancreatic polypeptide [9].
• These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes [10].

Chemical compound and disease context of Multiple Endocrine Neoplasia

• In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (> or = 116) of disease-associated mutations has been identified among patients with Hirschsprung disease and multiple endocrine neoplasia type 2 [11].
• A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A [12].
• Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior pituitary and other tissues [13].
• Recently the gene for multiple endocrine neoplasia type 1 was mapped to the long arm of chromosome 11 between the loci PGA and INT2 [14].
• Measurement of urinary epinephrine in screening for pheochromocytoma in multiple endocrine neoplasia type II [15].

Biological context of Multiple Endocrine Neoplasia

• A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma [16].
• The molecular pathology of somatotrophinomas has been investigated by a combined search for dominant mutations of the gene encoding the Gs alpha protein and for recessive mutations involving chromosome 11q13, which contains the gene causing multiple endocrine neoplasia type 1 (MEN1) [17].
• Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers [18].
• Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B [19].
• Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states [13].

Anatomical context of Multiple Endocrine Neoplasia

• METHODS: Ten kinase domain HSCR mutations were introduced into wild-type RET and constitutively activated RET with a multiple endocrine neoplasia 2A mutation, and the resulting mutant complementary DNAs were transfected into SK-N-MC primitive neuroectodermal tumor cells or NIH 3T3 fibroblast cells [20].
• Germ line missense mutations in the RET proto-oncogene are responsible for the inherited cancer syndrome multiple endocrine neoplasia type 2A (MEN2A) [21].
• RESULTS: In patients with sporadic ZES, but not in those with multiple endocrine neoplasia type 1 (MEN-1) and ZES, there was a significant relationship between the level of initial FSG and tumor size and location of primary tumor, frequency of lymph node and liver metastases, and survival [22].
• The basic fibroblast growth factor-like mitogen detected in the plasma of patients with the multiple endocrine neoplasia type 1 (MEN-1) syndrome was found to have a specific mitogenic effect on parathyroid endothelial cells in vitro [23].
• Gain-of-function mutations of ret receptor tyrosine kinase, the signaling receptor for glial cell line-derived neurotrophic factor, cause sporadic thyroid and adrenal malignancies as well as endocrine cancer syndromes, such as multiple endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma [24].

Gene context of Multiple Endocrine Neoplasia

• A model for GFR alpha 4 function and a potential modifying role in multiple endocrine neoplasia 2 [25].
• Germline high penetrance gain-of-function RET mutations cause multiple endocrine neoplasia type 2, of which medullary thyroid carcinoma (MTC) and pheochromocytoma are components, whereas loss-of-function mutations cause Hirschprung disease (HSCR) [26].
• Molecular analysis of the ret and GDNF genes in a family with multiple endocrine neoplasia type 2A and Hirschsprung disease [27].
• Multiple endocrine neoplasia type 1 (MEN1) is tightly linked to the muscle-type glycogen phosphorylase (PYGM) gene in 11q13 [28].
• Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate gene for multiple endocrine neoplasia type 1 (MEN1) [29].

Analytical, diagnostic and therapeutic context of Multiple Endocrine Neoplasia

• Primary hyperparathyroidism in familial multiple endocrine neoplasia type I. Long-term follow-up of serum calcium levels after parathyroidectomy [30].
• Diagnosis of multiple endocrine neoplasia [MEN] 2A, 2B and familial medullary thyroid cancer [FMTC] by multiplex PCR and heteroduplex analyses of RET proto-oncogene mutations [31].
• Plasma chromogranin A (CgA) has been claimed to be a sensitive marker for neuroendocrine tumors, but its role in the early diagnosis of multiple endocrine neoplasia type 1 (MEN 1) pancreatic endocrine tumors has not been evaluated [32].
• The histogenesis of pancreatic islet cell tumors was investigated by morphological identification of putative precursor lesions in pancreatic tissue from patients with multiple endocrine neoplasia type 1 (MEN1), tissue microdissection, and genetic analysis [33].
• Patients without metastatic disease and without the MEN-1 syndrome (multiple-endocrine-neoplasia type 1) should undergo exploratory laparotomy by a surgeon experienced in treating this disease, with studies suggesting a cure rate of approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)[34]

References