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

Carcinoids are well differentiated tumors, able to secrete a variety of bioactive and hormonal products. Neuroendocrine tumors occur either sporadically or as part of familial syndromes (MEN1, MEN2). Defective DNA mismatch repair is implicated in a variety of gastrointestinal and other cancers; however, its role in the tumorigenesis of carcinoids has not been assessed. Formalin-fixed, paraffin-embedded archivial pathology tissues from 16 neuroendocrine tumors and 9 related metastases were studied by microdissection and microsatellite analysis of extracted DNA to evaluate the degree of microsatellite instability, a marker of defective mismatch repair. The carcinoid tumors analyzed display no microsatellite instability, but, interestingly, show a number of allelic deletions scattered throughout the genome. Particularly, the vast majority of pancreatic derived tumors display loss of heterozygosity on the short arm of chromosome 8. These results suggest that genomic instability is probably not involved in neuroendocrine carcinogenesis and a tumor suppressor gene involved in pancreatic carcinoid tumorigenesis could probably be localized on chromosome 8p12-22.
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PMID:Microsatellite instability and allelic losses in neuroendocrine tumors of the gastro-entero-pancreatic system. 1040 48

Multiple endocrine neoplasia type 1 (MENI) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MENI mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MENI gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.
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PMID:The gene for multiple endocrine neoplasia type 1: recent findings. 1042 35

Pulmonary tumorlets are minute neuroendocrine cell proliferations believed to be precursor lesions to pulmonary carcinoids. Little is known of their molecular pathogenesis because of their small size. Using tissue microdissection, we evaluated 11q13 region allelic imbalance in the pathogenesis of pulmonary tumorlet/carcinoid lesions. The int-2 gene was selected because of its chromosomal location at 11q13 in close proximity to MEN1, a tumor suppressor gene frequently mutated in familial forms of neuroendocrine cancer. Three cohorts of patients were studied: subjects with typical carcinoid tumors and coexisting tumorlets (n = 5), typical carcinoids without tumorlets (n = 6), and tumorlets alone without carcinoid lesions (n = 5). A total of 11 carcinoids and 11 tumorlets were microdissected from 4-micrometer-thick histological sections. Genotyping was designed to detect allelic imbalance of the int-2 gene and involved DNA sequencing of two closely spaced deoxynucleotide polymorphisms. Subjects shown to be informative were evaluated for allelic imbalance in tumorlet/carcinoid tissue. Eight of 11 (73%) carcinoids manifested allelic, in contrast to only one of 11 (9%) of tumorlets. Int-2 allelic imbalance was significantly associated with carcinoid tumor formation (P < 0.01). In patients having both carcinoid tumors and tumorlets, the latter showed allelic balance and were thus discordant in genotype with coexisting carcinoid excluding pathogenesis of tumorlets from intramucosal spread from carcinoid tumors. Int-2 allelic imbalance was shown to be an early event in carcinoid tumor formation by virtue of the absence of allelic imbalance for other common cancer-related gene disturbances involving 11p13 (Wilms' tumor), 3p25 (von-Hippel-Lindau), and 17p13 (p53). Demonstration of 11q13 allelic imbalance by microdissection/genotyping may be a useful discriminatory marker for pulmonary neuroendocrine neoplasia.
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PMID:11q13 allelic imbalance discriminates pulmonary carcinoids from tumorlets. A microdissection-based genotyping approach useful in clinical practice. 1043 56

MEN1 is a syndrome of parathyroid adenomas, gastrinomas, prolactinomas, and other endocrine tumors. Collagenomas and facial angiofibromas are newly recognized but common skin expressions. Many tumors in MEN1 are benign; however, many entero-pancreatic neuroendocrine tumors and foregut carcinoid tumors are malignant. MEN1 is thus the expression of a cancer gene but without available prevention or cure for malignancy. Hereditary (as compared to sporadic) endocrine tumors show early onset age and multiplicity, because each cell of the body has "one hit" by inheritance. Multiple neoplasia syndromes with endocrine tumor(s) all include nonendocrine components; their known defective genes seem mainly to disturb cell accumulation. Hereditary neoplasia/hyperplasia of one endocrine tissue reflects a defect that is tissue selective and directed at cell secretion. Though the hereditary endocrine neoplasias are rare, most of their identified genes also contribute to common sporadic endocrine neoplasms. Hereditary tumors may be caused by activation of an oncogene (e.g., RET) or, more often, by inactivation of a tumor suppressor gene (e.g., P53, MEN1). Recently, MEN1 was identified by positional cloning. This strategy included narrowing the gene candidate interval, identifying many or all genes in that interval, and testing the newly identified candidate genes for mutation in MEN1 cases. MEN1 was identified because it showed mutation in 14 of 15 MEN1 cases. NIH testing showed germline MEN1 mutations in 47 of 50 MEN1 index cases and in seven of eight cases with sporadic MEN1. Despite proven capacity to find germline MEN1 mutation, NIH testing found no MEN1 mutation among five families with isolated hyperparathyroidism, suggesting that this often arises from mutation of other gene(s). Analogous studies in Japan found that familial isolated pituitary tumors also did not show MEN1 germline mutation. MEN1 mutation testing can now be considered for cases of MEN1 and its phenocopies and for asymptomatic members of families with known MEN1 mutation. Germline MEN1 testing does not have the urgency of RET testing in MEN2a and 2b, as MEN1 testing does not commonly lead to an important intervention. Somatic MEN1 mutation was found in sporadic tumors: parathyroid adenoma (21%), gastrinoma (33%), insulinoma (17%), and bronchial carcinoid (36%). For each of these, MEN1 was the known gene most frequently mutated. MEN1 has a widely expressed mRNA that encodes a protein (menin) of 610 amino acids. The protein sequence is not informative about domains or functions. The protein was mainly nuclear. Menin binds to JunD, an AP-1 transcription factor, inhibiting JunD's activation of transcription. Most of the germline and somatic MEN1 mutations predict truncation of menin, a likely destructive change. Inactivating MEN1 mutations in germline and in sporadic neoplasms support prior predictions that MEN1 is a tumor suppressor gene. Germline MEN1 mutation underlies all or most cases of MEN1 (familial or sporadic). Somatic MEN1 mutation is the most common gene mutation in many sporadic endocrine tumor types.
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PMID:Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neoplasias. 1054 85

The MEN1 gene locus is known to be partly responsible for the tumorigenesis of sporadic gastric neuroendocrine tumors, but the genetic events that drive the neoplastic process of this tumor remain largely unknown. In order to screen the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors, 15 neuroendocrine carcinomas and three carcinoid tumors in the stomach were analyzed for loss of heterozygosity (LOH) using 22 microsatellite markers. In our study, the gastric neuroendocrine tumors showed a high rate of LOH in chromosomes 8p (82%), 15q (58%), 17p (57%), llp (50%), 12p (50%) and 13q (50%). The mean fractional allelic loss (FAL) was higher in the neuroendocrine carcinoma components than in the adenocarcinoma components (0.42 versus 0.33, respectively). In four cases, the adenocarcinoma components showed discordant LOH patterns from those of the neuroendocrine counterparts in half of the informative chromosomes analyzed. Comparably, the gastric neuroendocrine carcinomas exhibited a higher LOH frequency on 8p and a lower LOH on 7q than did the gastric adenocarcinomas. It is suggested that chromosome 8p is the possible location of the tumor suppressor genes associated with the tumorigenesis of gastric neuroendocrine tumors.
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PMID:Loss of heterozygosity in gastric neuroendocrine tumor. 1106 92

MEN-1 is an autosomal dominantly inherited disorder, characterised by the occurrence of multiple tumours, particularly in the parathyroid glands, the pancreatic islets, the pituitary gland and the adrenal glands, as well as by neuroendocrine carcinoid tumours. Various clinical manifestations are presented by description of three patients harbouring a MEN1 gene germline mutation. A 44-year-old man had symptoms of hyperparathyroidism and in addition to parathyroid adenomas proved to have tumours in the thymus, adrenal and pituitary glands. A 48-year-old woman from a family with MEN-1 had suffered since her 40th year from headache and heartburn; she appeared to have adenomas in the parathyroid glands and gastrinomas in the pancreas, leading to a Zollinger-Ellison syndrome. One of her relatives, a man aged 29, had suffered from childhood from convulsions due to attacks of hypoglycaemia, and an insulinoma was assessed. In all patients, surgical and/or medical treatment alleviated symptoms. Clearly, the position or nature of the mutations in the MEN1 gene do not correlate with the clinical expression of the disease. Family investigation, DNA analysis and periodic examination improve quality of life and the life expectancy.
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PMID:[Diverse expression of multiple endocrine neoplasia type 1]. 1115 52

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominantly inherited disorder, characterised by the occurrence of multiple tumours, particularly in the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as neuroendocrine carcinoid tumours. Since the identification of the responsible gene in 1997, the diagnosis MEN-1 can be assessed easily, and even presymptomatically, by DNA analysis. An early diagnosis is of importance because through periodic clinical monitoring of (putative) MEN1 gene germline mutation carriers, tumour development can be detected and treated at an early stage. Eligible for DNA analysis are MEN-1 patients and their family members, as well as patients with seemingly sporadic MEN-1 related tumours in whom on clinical grounds carriership of a MEN1 gene germline mutation is suspected. Eligible for periodic clinical monitoring are putative and confirmed carriers of a MEN1 germline mutation from the age of 5.
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PMID:[Multiple endocrine neoplasia type 1: recent developments and guidelines for DNA diagnosis and periodic clinical monitoring]. 1115 50

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

Carcinoid tumors are rare neoplasms which, by tradition, have been divided into foregut, midgut, and hindgut tumors. Although they share many features, they seem to have different molecular backgrounds. Foregut tumors very often show involvement of the MEN1 gene with deletions and mutations, whereas midgut carcinoids display genetic changes on chromosome 18. Hindgut tumors in general show rather low proliferation capacity, and transforming growth factor-alpha/epidermal growth factor receptor autocrine mechanism may play a role in the tumor development. Sometimes it might be a problem to delineate the location of the primary carcinoid tumor, but analyzing thyroid transcription factor-1 can be of help, because this factor is only expressed in foregut carcinoid and not in midgut or hindgut tumors. Chromogranin A is an important general tumor marker for all types of carcinoid tumors. Somatostatin receptor scintigraphy is a cornerstone in staging and localization of carcinoid tumors, but newer techniques such as positron emission tomography will challenge its position in the future. Although surgical cure is not obtainable, a more aggressive surgery has emerged during the last decade. Debulking and other cytoreductive procedures are quite common today. Somatostatin analogues have been the treatment of choice in symptomatic patients with carcinoid tumors, but more recent studies have indicated a cytostatic effect of somatostatin analogues. Tumor-targeted radioactive treatment based on somatostatin analogues is now under clinical evaluation. Preliminary data indicate interesting clinical potentials.
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PMID:Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. 1179 Sep 79

A pancreas carcinoid, an adrenocortical adenoma, three parathyroid adenomas and a parathyroid hyperplasia of 5 MEN1 patients were used for loss of heterozygosity (LOH) and comparative genomic hybridization (CGH) studies. The MEN1 gene is located in the region 11q13, approximately 30 kb distal to PGYM. Four tumors showed LOH on chromosome 11q13 (D11S11335, PGYM, D11S1883, FGF3, D11S937) however LOH was also found beyond 11q13. The pancreas carcinoid and adrenocortical adenoma, both from the same patient, showed LOH at marker 11q23.3 and 11q25. In the three parathyroid adenomas LOH was detected in five different markers: 11q21, 11q22.3, 11q23.2, 11q23.3 and 11q25. No LOH was found in parathyroid hyperplasia. CGH analysis showed in case of the pancreas carcinoid losses on chromosomes 1p, 2q, 3, 6, 9p, 11 and 12p. Gains were found at 4, 5, 7, 8, 13, 14, 15q, 18, 19. The parathyroid adenoma of the third patient showed losses only on chromosome 11 in the region 11p12-p15 and 11q12-q23. Our data indicate that other genes are involved in the tumorigenesis of the MEN1 syndrome. Especially the numerous allelic losses between markers 11q23 and 11q25 (D11S938 and D11S910) are a hint for further tumor suppressor genes on chromosome 11.
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PMID:Cytogenetic and molecular analyses of multiple endocrine neoplasias of the MEN1 syndrome. 1195 91


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