Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by parathyroid, pancreatic, and anterior pituitary tumors.
A subset of patients carry germline mutations in genes such as MEN1 (multiple endocrine neoplasia type 1), HRPT2 (hyperparathyroidism 2), and CASR (calcium-sensing receptor) predisposing to syndromic forms of PHPT or familial isolated hyperparathyroidism (FIHP).
We aim to analyze MEN1 mutation site and features, and possible correlations between the mutation type and/or the affected menin functional domain and clinical presentation in patients from the Italian multicenter MEN1 database, one of the largest worldwide MEN1 mutation series published to date.
We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.
Since its isolation, several groups have begun to determine the role of menin, the protein product of MEN1, in sporadic endocrine tumors as well as tumors of the MEN1 syndrome.
Ten subjects (45.5%) have not yet presented any clinical/biochemical/radiological manifestation of MEN1 disease, whereas 12 patients (54.5%) developed at least one MEN1-associated endocrine manifestation.
Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1).
Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs.
The mean age of MEN1 phenocopy patients (including variants) at diagnosis was 48 yr, which was not significantly different from that of probands of familial MEN1 (46 yr) who carry heterozygous MEN1 gene mutations.
We also investigated if genes were differentially expressed in 6 malignant endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation compared to 2 without MEN1 gene alterations.
To elucidate the potential etiological role of the MEN1 gene in pituitary tumorigenesis, 39 sporadic pituitary adenomas from 38 patients and 1 pituitary adenoma from a familial MEN1 patient were examined for MEN1 gene mutations and allelic deletions.
Mutation screening of the MEN1 gene using CSGE was demonstrated to be a fast, simple, and inexpensive method to study patients suspected of having MEN1 disease.
Mutation screening of the MEN1 gene has been recommended for patients who meet clinical criteria for MEN1 (at least two of the following: parathyroid hyperplasia, pancreatic endocrine tumour or pituitary adenoma) and those in whom a diagnosis of MEN1 is suspected.
PubMed was searched for English language articles, and words used were: MEN1 OR MEN-1 OR MEN type 1 OR multiple endocrine neoplasia 1 OR multiple endocrine neoplasia type 1 AND Mutational analysis OR genetic testing OR testing OR Hyperparathyroidism, primary [majr].A total of 625 abstracts were reviewed.
Menin is a protein product of a tumor suppressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome.
The lack of obvious LOH of the MEN1 locus in the papillary cancer suggests that, in contrast to parathyroid adenoma, deletion of the MEN1 tumor suppressor gene is not etiologically related to the oncogenesis of the papillary cancer in this patient.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes.
Primary hyperparathyroidism is usually expressed at an early age and is highly penetrated in MEN type 1 (MEN1), suggesting that some FHP may be a variant type or early stage of MEN1.
The expression of neurogenin 3 (NEUROG3), neurogenic differentiation 1 (NEUROD1), POU class 3 homeobox 4 (POU3F4), pancreatic duodenal homeobox factor 1 (PDX1), ribosomal protein L10 (RPL10), delta-like 1 homolog (Drosophila; DLK1), and menin was analyzed by immunohistochemistry in normal pancreas and pancreatic endocrine tumors from 6 patients with MEN1 and 16 patients with sporadic tumors, as well as pancreatic specimens from Men1 heterozygous and wild type mice.