Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors have been described only in the small genetically defined subgroup of patients who have the multiple endocrine neoplasia type 1 syndrome (MEN-1). Allelic losses on 11q13, on which MEN-1 gene has been localized, have been noted in parathyroid and pancreatic tumors of patients with MEN-1, suggesting that the MEN-1 gene could act as a recessive tumor suppressor gene. One fundic argyrophil carcinoid tumor from a patient with the Zollinger-Ellison syndrome and MEN-1 was studied. Loss of heterozygosity in the tumor DNA at loci close to MEN-1 locus was looked for using Southern technique with six DNA probes. Segregation of alleles was examined in relatives. In the tumor DNA, we found the loss of one allele with PYGM, the closest probe to the MEN-1 locus. The allele lost in the tumor had been transmitted by the unaffected parent. This suggests that in patients with the Zollinger-Ellison syndrome and MEN-1, the promotion of fundic argyrophil carcinoid tumors results from the inactivation of the two copies of MEN-1 gene and that fundic argyrophil carcinoid tumors may be included in the spectrum of MEN-1-related tumors.
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PMID:Is the multiple endocrine neoplasia type 1 gene a suppressor for fundic argyrophil tumors in the Zollinger-Ellison syndrome? 810 1

Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors as well as foregut carcinoids in affected patients. The gene responsible for the disease has been linked to chromosome 11q13. We analyzed loss of heterozygosity (LOH) in 188 tumors from 81 patients in an attempt to further define the location of the MEN1 gene. Both tumors from MEN1 patients and corresponding sporadic tumors were analyzed. Tumor types included parathyroid, gastrinoma, pancreatic endocrine, pituitary, and lung carcinoid. Six tumors (three MEN1 and three sporadic tumors) were identified that provided important LOH boundaries. Four tumors (two parathyroid tumors, one gastrinoma, and one lung carcinoid tumor) showed allelic loss that placed the MEN1 gene distal to marker PYGM. Two tumors (one gastrinoma and one parathyroid tumor) showed an LOH boundary that placed the gene proximal to D11S449, one of which further moved the telomeric boundary to D11S4936. Taken together, the present data suggest that the MEN1 gene lies between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13.
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PMID:Localization of the multiple endocrine neoplasia type I (MEN1) gene based on tumor loss of heterozygosity analysis. 915 74

To clarify the role of the MEN1 gene in the tumorigenesis of sporadic adrenocortical tumors, we performed a molecular study on 35 adrenocortical lesions including 6 hyperplasias, 19 adenomas and 10 carcinomas. Loss of heterozygosity (LOH) of the MEN1 gene was assessed by PCR using an intragenic (D11S4946) and 2 flanking microsatellite markers (D11S4936, PYGM) and/or fluorescence in situ hybridization (FISH) with a 40-kb cosmid probe containing the MEN1 gene. The complete coding sequence of the MEN1 gene was screened for mutations using non-radioactive, PCR-based single-strand conformation polymorphism (SSCP) analysis and MDE heteroduplex gel electrophoresis. PCR-LOH and FISH analyses performed in 29 tumors (PCR-LOH in 4, FISH in 17 and both in 8 tumors) revealed allelic deletion of the MEN1 locus in 8 (27.5%) and at 11q13 in 9 (31%) tumors. Furthermore, the frequency of LOH at 11q13 was significantly higher in adrenocortical carcinomas (60%) than in benign lesions (11%). Mutation analysis of tumor samples revealed 9 polymorphisms in 7 tumors (S145S, R171Q, R171Q together with L432L) but no mutations, with the exception of one adrenocortical adenoma. The latter tumor contained a somatic E109X stop codon mutation in exon 2 and a 5178-9G-->A splice mutation in intron 4, which was also detectable in various nontumorous tissues and blood indicative of a germ-line mutation. The patient, who had no clinical signs or family history of MEN1, later also developed a neuroendocrine carcinoma (atypical carcinoid) of the lung. Our findings indicate that inactivating mutations of the MEN1 tumor-suppressor gene appear not to play a prominent role in the development of sporadic hyperplastic or neoplastic lesions of the adrenal cortex and that the newly reported 5178-9G-->A splice mutation in intron 4 might cause a variant of the MEN1 phenotype.
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PMID:MEN1 gene mutation analysis of sporadic adrenocortical lesions. 1086 92

Loss of heterozygosity (LOH) at the MEN1 gene locus at 11q13 is commonly found in type II gastric carcinoid tumors, which are associated with multiple endocrine neoplasia type 1 (MEN-1). In contrast, information is scanty or absent for other types of gastric neuroendocrine tumors, represented by type I carcinoids (associated with chronic atrophic gastritis), type III (sporadic) carcinoids, and neuroendocrine carcinomas. Moreover, LOH analysis of the allelic region distal to the MEN1 gene, which is postulated to contain an additional tumor suppressor gene effective in MEN-1-associated and sporadic endocrine tumors, has never been performed. To clarify these issues, DNA extracted from archival tissue from 25 type I carcinoids, 4 type III carcinoids, and 2 neuroendocrine carcinomas was amplified by PCR, using primers for six polymorphic markers located on chromosome 11q13 (PYGM, D11S4946, and D11S913) and 11q14 (D11S916, D11S901, and D11S1365), for analysis of LOH. Allelic losses in the 11q13-14 region with at least two polymorphic markers were found in 12 of 25 (48%) type I carcinoids. When LOH was found in the 11q13 region, it was large and continuous and extended to the most telomeric marker investigated. In one tumor, retention of heterozygosity for markers in the MEN1 region and LOH for distal markers were observed. No LOH was found in three of four type III carcinoids. Large deletions in both the 11q13 and 11q14 regions were observed in both neuroendocrine carcinomas investigated. In conclusion, LOH in the 11q13-14 regions is frequently found in type I carcinoids and neuroendocrine carcinomas of the stomach, suggesting the involvement of the MEN1 gene and/or a more telomeric tumor suppressor gene in the pathogenesis of these non-MEN-1-associated neuroendocrine tumors. The low rate of LOH at 11q13-14 suggests the predominance of different genetic mechanisms in type III carcinoids, which also differ from other types of gastric carcinoids in the lack of a promoter role for gastrin.
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PMID:Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. 1037 9

Neuroendocrine lung tumors such as typical carcinoid, atypical carcinoid, small-cell lung carcinoma, and large-cell neuroendocrine carcinoma represent a variable group with different biologic characteristics and unclear genetical relationships. We investigated the pattern of allelic loss on chromosome arm 11q in 20 sporadic carcinoid tumors of the lung using 10 microsatellite markers. Loss of heterozygosity was found in 13 of 20 tumors. In 5 of 9 typical carcinoids, 3 distinct regions of allelic loss were identified: 11q13.1 (D11S1883), 11q14.3-11q21 (D11S906), and 11q25 (D11S910). Atypical carcinoids showed loss of heterozygosity at 4 different regions: the first, most proximal region at 11q13 between markers PYGM and D11S937; the second at 11q14.3-11q21 (D11S906); and the third and fourth defined by markers D11S939 (11q23.2-23.3) and D11S910 (11q25). However, the region 11q13 harboring the MEN1 gene was more frequently affected in atypical carcinoids (7 of 11) than in typical carcinoids (2 of 9). The high rate of allelic losses within chromosomal region 11q13 in atypical carcinoids emphasizes the importance of this region for tumor development. We also recognized that more aggressive atypical carcinoids defined by high mitotic counts, vascular invasion, and/or organ metastasis are combined with increased allelic losses. HUM PATHOL 32:333-338.
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PMID:Loss of heterozygosity on chromosome arm 11q in lung carcinoids. 1127 44

The possible causes and genetic mechanisms of pulmonary carcinoid tumor development are unclear. In this study, we examined genetic alterations at the MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for the first time in this setting, real-time PCR with melting curve analysis in order to identify loss of heterozygosity (LOH) or microsatellite instability (MI) in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene. Sequencing data were available in a selected subset of tumors in order to verify the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with melting curve analysis is a reliable technique for LOH and MI detection and indicate that genetic errors at the MEN1 locus but also distal to it may be involved in the development of sporadic pulmonary carcinoid tumors.
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PMID:Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: a novel approach using real-time PCR with melting curve analysis in histopathologic material. 1646 12