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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.
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PMID:Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. 936 Oct 35

Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100, Wermer syndrome) is characterized by inherited predisposition to primary hyperparathyroidism, endocrine pancreatic-duodenal, pituitary, adrenal glands tumors and benign and/or malignant proliferations of diffuse neuroendocrine tumors in thymus and bronchi, formerly defined as carcinoid tumors. Minor lesions have been observed in MEN1 patients such as cutaneous tumors (angiofibroma, lipoma, lentiginosis), thyroid epithelioma and tumors of the central nervous system, mainly spinal ependymoma. The MEN1 gene, a locus encompassing a 9 kb of genomic sequence contains 10 exons, the first exon being untranslated. The protein encoded by this gene was called menin and has been shown to contain two nuclear localization signals (NLS), suggesting a major function in the nucleus. Germline MEN1 mutations have been described in more than 150 families and are spread throughout the entire coding sequence. More than 70% of the mutations alter one or both NLS and no genotype-phenotype correlations were found to date. The MEN1 gene seems to be involved in a 20-30% of sporadic parathyroid and pancreatic/bronchic neuroendocrine tumors, but less than 1% of pituitary sporadic tumors. Further knowledge on the intracellular function of menin will be needed to understand the pathogenic effect of truncating and missense mutations of this gene in the initiation of endocrine cells tumorigenesis.
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PMID:[Clinicogenetic study of MEN1: recent physiopathological data and clinical applications. Study Group of Multiple Endocrine Neoplasia (GENEM)]. 1018 86

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been cloned, and its germline mutations were identified in patients with this syndrome. The majority of the mutations, frameshift or nonsense mutations, are expected to result in a loss of function of the gene product menin. Since the consequence of less common missense or in-frame deletion mutations is not clear, careful judgment is necessary regarding the role(s) of such mutations in MEN1 disease. Here we describe a large multigenerational MEN1 family with a novel germline missense mutation and three benign polymorphisms. The proband was a man with hyperparathyroidism and thymic carcinoid. We performed biochemical studies and DNA analyses of the MEN1 gene simultaneously and independently as family screening studies. Seven patients including the proband were identified, and all of them carried a heterozygous germline missense mutation E45G, but 5 members with normal biochemical results did not. This mutation was not observed in 50 normal volunteers. This novel missense mutation is therefore almost conclusively responsible for the disease. Although all of the mutant gene carriers in the present study already had clinical diseases, an MEN1 gene analysis in younger individuals at risk would be very useful in identifying carriers before the onset of the symptoms.
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PMID:A family of MEN1 with a novel germline missense mutation and benign polymorphisms. 1039 30

Multiple endocrine neoplasia type 1 (MEN1) provides a prime example of how a rare disease can advance our understanding of basic cell biology, neoplasia and common endocrine tumors. MEN1 is expressed mainly as parathyroid, enteropancreatic neuroendocrine, anterior pituitary and foregut carcinoid tumors. It is an autosomal dominant disease caused by mutation of the MEN1 gene. Since its identification, the MEN1 gene has been implicated in many common endocrine and non-endocrine tumors. This is a brief overview of recent scientific advances relating to MEN1, including newly recognized clinical features that are now better characterized by genetic analysis, insights into the function of the MEN1-encoded protein menin, and refined recommendations for mutation testing and tumor screening, which highlight our increasing understanding of this complex syndrome.
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PMID:Multiple endocrine neoplasia type 1: new clinical and basic findings. 1129 74

Multiple endocrine neoplasia type 1 (MEN-1) is an interesting genetic syndrome of polyendocrinopathies. Clinical knowledge about MEN-1 is essential as it appears to be significantly under-diagnosed. New data from several prospective series shows not only that as a many as 40% of patients manifest a first feature of MEN-1 after age 40, but also that as many as a third of gene carriers do not present with hyperparathyroidism as the first feature, as previously believed. Mutational analysis for frequently involved exons of the gene menin on chromosome 11 is now available, but negative results should be interpreted with caution in patients with clinical MEN-1. Disease-specific mortality is significant, arises largely from pancreatic islet carcinoma and malignant thymic carcinoid, and renders this disorder worthy of careful and early prospective diagnosis and treatment.
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PMID:Multiple endocrine neoplasia type 1: fresh perspective on clinical features and penetrance. 1235 10

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.
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PMID:Endocrine tumours of the stomach. 1625 92

Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were found in 68 patients with other fore-/midgut endocrine tumours. Moreover, screening of 60 consecutive patients with primary prolactinoma did not identify any mutation carriers. Our data indicate that MEN1 mutation screening is efficient in patients with familial MEN1. Screening should also be offered to patients with pHPT or gastrinomas after thorough investigation into the family history. In contrast, sporadic carcinoid tumours or primary prolactinomas are rarely associated with germ-line MEN1 mutations.
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PMID:Characteristics of the Danish families with multiple endocrine neoplasia type 1. 1656 11

Thymic carcinoid is a rare multiple endocrine neoplasia type 1 (MEN1)-associated tumour that is a major cause of death in MEN1 patients. Here, we describe a previously unreported MEN1 family in which two siblings presented with malignant thymic carcinoids. All six siblings share a novel nonsense mutation Q395X on exon 8 of the MEN1 gene. The index patient developed a thymic carcinoid despite an earlier prophylactic transcervical thymectomy, and one other sibling had an incidental malignant thymic carcinoid discovered following prophylactic thymectomy, both cases demonstrating the weakness and strength of this surgical approach. We then review the spectrum of germline MEN1 mutations associated with thymic carcinoids to evaluate the possibility of a genotype-phenotype correlation. In the 22 separate MEN1 families with thymic carcinoids, all but two (91%) have mutations coding for a truncated protein. There is clearly a high prevalence of truncating mutations in MEN1-related thymic carcinoids although when compared with the prevalence of truncating mutations in all reported MEN1 mutations, it is not statistically significant (P = 0.39). Further studies are warranted to evaluate pathways of tumorigenesis of thymic carcinoids with regard to loss of function of menin.
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PMID:Thymic carcinoid in multiple endocrine neoplasia 1: genotype-phenotype correlation and prevention. 1659 11

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The product of the MEN1 gene is the nuclear protein menin. Recent observations indicate several functions for menin in the regulation of transcription, serving either as a repressor or as an activator: menin interacts with the activator-protein-1-family transcription factor JunD, changing it from an oncoprotein into a tumor-suppressor protein, putatively by recruitment of histone deacetylase complexes; menin maintains transforming growth factor beta mediated signal transduction involved in parathyroid hormone and prolactin gene expression; and menin is an integral component of histone methyltransferase complexes. In this capacity menin is a regulator of expression of the cyclin-dependent-kinase inhibitors p18INK4C and p27Kip1; furthermore, menin serves as a co-activator of estrogen receptor mediated transcription, by recruiting methyltransferase activity to lysine 4 of histone 3 at the estrogen responsive TFF1(pS2) gene promoter. We propose that menin links transcription-factor function to histone-modification pathways and that this is crucial for MEN1 tumorigenesis. Understanding the molecular pathology of MEN1 tumorigenesis will lead to new therapeutic strategies.
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PMID:Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation. 1702 55

The rare association between Von Recklin-ghausen's disease (VRD) and tumours other than in central nervous system is well recognized. However, the concomitance of VRD, a carcinoid of the ampulla of Vater, and a pheochromocytoma has been described very rarely in literature. Furthermore, the possible role of the genes usually involved in multiple endocrine neoplasia (MEN) syndromes, in this association, is unclear. We report the case of a patient affected by VRD and extra-adrenal pheochromocytoma, operated on in the past for a carcinoid of the ampulla of Vater. To determine if genes involved in MEN syndromes might play a role in this particular triad, we investigated the presence of somatic or germline mutations in the RET proto-oncogene and menin gene by non isotopic polymerase chain reaction single stranded conformation polymorphism (PCR-SSCP) and heteroduplex gel electro-phoresis. The results demonstrated that no somatic or germline mutations in the MEN-1 and MEN-2 genes were involved in the pathogenesis of these tumours.
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PMID:Absence of gene mutations in a case of concomitant presence of carcinoid of the ampulla of vater pheochromocytoma and Von Recklinghausen disease. 1710 73


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