PubMed:10496602
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/10496602","sourcedb":"PubMed","sourceid":"10496602","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10496602","text":"Multiple endocrine neoplasia type 1: atypical presentation, clinical course, and genetic analysis of multiple tumors.\nMultiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. The pathogenesis of non-neuroendocrine tumors in MEN1 is unknown. We report a complex clinical course and a detailed morphologic and genetic analysis of a series of tumors that developed in a patient with MEN1. All tumors were microdissected and analyzed for loss of heterozygosity of the MEN1 gene. A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's \"two hit\" hypothesis. Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1. In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1-associated tumors.","tracks":[{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":117},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":118,"end":281},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":282,"end":399},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":400,"end":585},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":586,"end":651},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":652,"end":796},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":797,"end":885},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":886,"end":1173},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1174,"end":1335},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1336,"end":1582},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":1583,"end":1710},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":117},"obj":"Sentence"},{"id":"T2","span":{"begin":118,"end":281},"obj":"Sentence"},{"id":"T3","span":{"begin":282,"end":399},"obj":"Sentence"},{"id":"T4","span":{"begin":400,"end":585},"obj":"Sentence"},{"id":"T5","span":{"begin":586,"end":651},"obj":"Sentence"},{"id":"T6","span":{"begin":652,"end":796},"obj":"Sentence"},{"id":"T7","span":{"begin":797,"end":885},"obj":"Sentence"},{"id":"T8","span":{"begin":886,"end":1173},"obj":"Sentence"},{"id":"T9","span":{"begin":1174,"end":1335},"obj":"Sentence"},{"id":"T10","span":{"begin":1336,"end":1582},"obj":"Sentence"},{"id":"T11","span":{"begin":1583,"end":1710},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T11","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":127,"end":146},"obj":"HP_0100568"},{"id":"T2","span":{"begin":137,"end":146},"obj":"HP_0002664"},{"id":"T3","span":{"begin":210,"end":216},"obj":"HP_0002664"},{"id":"T4","span":{"begin":210,"end":235},"obj":"HP_0006780"},{"id":"T5","span":{"begin":210,"end":256},"obj":"HP_0100733"},{"id":"T6","span":{"begin":308,"end":314},"obj":"HP_0002664"},{"id":"T7","span":{"begin":358,"end":364},"obj":"HP_0002664"},{"id":"T8","span":{"begin":373,"end":380},"obj":"HP_0012032"},{"id":"T9","span":{"begin":385,"end":398},"obj":"HP_0010615"},{"id":"T10","span":{"begin":434,"end":443},"obj":"HP_0002664"},{"id":"T11","span":{"begin":526,"end":546},"obj":"HP_0006772"},{"id":"T12","span":{"begin":532,"end":546},"obj":"HP_0006772"},{"id":"T13","span":{"begin":610,"end":631},"obj":"HP_0100634"},{"id":"T14","span":{"begin":625,"end":631},"obj":"HP_0002664"},{"id":"T15","span":{"begin":751,"end":757},"obj":"HP_0002664"},{"id":"T16","span":{"begin":801,"end":807},"obj":"HP_0002664"},{"id":"T17","span":{"begin":1007,"end":1028},"obj":"HP_0100634"},{"id":"T18","span":{"begin":1022,"end":1028},"obj":"HP_0002664"},{"id":"T19","span":{"begin":1093,"end":1113},"obj":"HP_0100634"},{"id":"T20","span":{"begin":1108,"end":1113},"obj":"HP_0002664"},{"id":"T21","span":{"begin":1349,"end":1375},"obj":"HP_0011774"},{"id":"T22","span":{"begin":1360,"end":1375},"obj":"HP_0000854"},{"id":"T23","span":{"begin":1377,"end":1404},"obj":"HP_0002895"},{"id":"T24","span":{"begin":1387,"end":1404},"obj":"HP_0002890"},{"id":"T25","span":{"begin":1600,"end":1606},"obj":"HP_0002664"},{"id":"T26","span":{"begin":1703,"end":1709},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"},{"subj":"T7","pred":"source","obj":"PubmedHPO"},{"subj":"T8","pred":"source","obj":"PubmedHPO"},{"subj":"T9","pred":"source","obj":"PubmedHPO"},{"subj":"T10","pred":"source","obj":"PubmedHPO"},{"subj":"T11","pred":"source","obj":"PubmedHPO"},{"subj":"T12","pred":"source","obj":"PubmedHPO"},{"subj":"T13","pred":"source","obj":"PubmedHPO"},{"subj":"T14","pred":"source","obj":"PubmedHPO"},{"subj":"T15","pred":"source","obj":"PubmedHPO"},{"subj":"T16","pred":"source","obj":"PubmedHPO"},{"subj":"T17","pred":"source","obj":"PubmedHPO"},{"subj":"T18","pred":"source","obj":"PubmedHPO"},{"subj":"T19","pred":"source","obj":"PubmedHPO"},{"subj":"T20","pred":"source","obj":"PubmedHPO"},{"subj":"T21","pred":"source","obj":"PubmedHPO"},{"subj":"T22","pred":"source","obj":"PubmedHPO"},{"subj":"T23","pred":"source","obj":"PubmedHPO"},{"subj":"T24","pred":"source","obj":"PubmedHPO"},{"subj":"T25","pred":"source","obj":"PubmedHPO"},{"subj":"T26","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10496602-7#72#76#gene4221","span":{"begin":958,"end":962},"obj":"gene4221"},{"id":"10496602-7#121#142#diseaseC0206754","span":{"begin":1007,"end":1028},"obj":"diseaseC0206754"},{"id":"10496602-7#199#227#diseaseC1333963","span":{"begin":1085,"end":1113},"obj":"diseaseC1333963"},{"id":"10496602-8#16#20#gene4221","span":{"begin":1190,"end":1194},"obj":"gene4221"},{"id":"10496602-8#48#68#diseaseC0238114","span":{"begin":1222,"end":1242},"obj":"diseaseC0238114"},{"id":"10496602-8#156#160#diseaseC0025267","span":{"begin":1330,"end":1334},"obj":"diseaseC0025267"},{"id":"10496602-9#189#193#gene4221","span":{"begin":1525,"end":1529},"obj":"gene4221"},{"id":"10496602-9#109#137#diseaseC0342494","span":{"begin":1445,"end":1473},"obj":"diseaseC0342494"}],"relations":[{"id":"72#76#gene4221121#142#diseaseC0206754","pred":"associated_with","subj":"10496602-7#72#76#gene4221","obj":"10496602-7#121#142#diseaseC0206754"},{"id":"72#76#gene4221199#227#diseaseC1333963","pred":"associated_with","subj":"10496602-7#72#76#gene4221","obj":"10496602-7#199#227#diseaseC1333963"},{"id":"16#20#gene422148#68#diseaseC0238114","pred":"associated_with","subj":"10496602-8#16#20#gene4221","obj":"10496602-8#48#68#diseaseC0238114"},{"id":"16#20#gene4221156#160#diseaseC0025267","pred":"associated_with","subj":"10496602-8#16#20#gene4221","obj":"10496602-8#156#160#diseaseC0025267"},{"id":"189#193#gene4221109#137#diseaseC0342494","pred":"associated_with","subj":"10496602-9#189#193#gene4221","obj":"10496602-9#109#137#diseaseC0342494"}],"attributes":[{"subj":"10496602-7#72#76#gene4221","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-7#121#142#diseaseC0206754","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-7#199#227#diseaseC1333963","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-8#16#20#gene4221","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-8#48#68#diseaseC0238114","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-8#156#160#diseaseC0025267","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-9#189#193#gene4221","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10496602-9#109#137#diseaseC0342494","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1243,"end":1249},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":1043,"end":1061},"obj":"http://purl.obolibrary.org/obo/UBERON_0001132"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":250,"end":256},"obj":"http://purl.obolibrary.org/obo/UBERON_0002530"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":1055,"end":1061},"obj":"http://purl.obolibrary.org/obo/UBERON_0002530"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":240,"end":256},"obj":"http://purl.obolibrary.org/obo/UBERON_0000007"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":258,"end":266},"obj":"http://purl.obolibrary.org/obo/UBERON_0001264"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":1070,"end":1078},"obj":"http://purl.obolibrary.org/obo/UBERON_0001264"},{"id":"PD-UBERON-AE-B_T8","span":{"begin":272,"end":280},"obj":"http://purl.obolibrary.org/obo/UBERON_0002114"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T8","pred":"source","obj":"performance-test"}]},{"project":"PubCasesHPO","denotations":[{"id":"AB1","span":{"begin":373,"end":380},"obj":"HP:0012032"},{"id":"AB2","span":{"begin":385,"end":398},"obj":"HP:0010615"},{"id":"AB3","span":{"begin":434,"end":443},"obj":"HP:0002664"},{"id":"AB4","span":{"begin":526,"end":546},"obj":"HP:0006772"},{"id":"AB5","span":{"begin":1360,"end":1375},"obj":"HP:0000854"},{"id":"AB6","span":{"begin":1377,"end":1404},"obj":"HP:0002895"}],"attributes":[{"subj":"AB1","pred":"source","obj":"PubCasesHPO"},{"subj":"AB2","pred":"source","obj":"PubCasesHPO"},{"subj":"AB3","pred":"source","obj":"PubCasesHPO"},{"subj":"AB4","pred":"source","obj":"PubCasesHPO"},{"subj":"AB5","pred":"source","obj":"PubCasesHPO"},{"subj":"AB6","pred":"source","obj":"PubCasesHPO"}]},{"project":"PubCasesORDO","denotations":[{"id":"TI1","span":{"begin":0,"end":35},"obj":"ORDO:652"},{"id":"AB1","span":{"begin":155,"end":159},"obj":"ORDO:652"},{"id":"AB2","span":{"begin":331,"end":335},"obj":"ORDO:652"},{"id":"AB3","span":{"begin":569,"end":573},"obj":"ORDO:652"},{"id":"AB4","span":{"begin":635,"end":639},"obj":"ORDO:652"},{"id":"AB5","span":{"begin":791,"end":795},"obj":"ORDO:652"},{"id":"AB6","span":{"begin":875,"end":879},"obj":"ORDO:652"},{"id":"AB7","span":{"begin":913,"end":917},"obj":"ORDO:652"},{"id":"AB8","span":{"begin":958,"end":962},"obj":"ORDO:652"},{"id":"AB9","span":{"begin":1157,"end":1160},"obj":"ORDO:3325"},{"id":"AB10","span":{"begin":1178,"end":1182},"obj":"ORDO:3325"},{"id":"AB11","span":{"begin":1190,"end":1194},"obj":"ORDO:652"},{"id":"AB12","span":{"begin":1330,"end":1334},"obj":"ORDO:652"},{"id":"AB13","span":{"begin":1525,"end":1529},"obj":"ORDO:652"},{"id":"AB14","span":{"begin":1687,"end":1691},"obj":"ORDO:652"}],"namespaces":[{"prefix":"ORDO","uri":"http://www.orpha.net/ORDO/Orphanet_"}],"attributes":[{"subj":"TI1","pred":"source","obj":"PubCasesORDO"},{"subj":"AB1","pred":"source","obj":"PubCasesORDO"},{"subj":"AB2","pred":"source","obj":"PubCasesORDO"},{"subj":"AB3","pred":"source","obj":"PubCasesORDO"},{"subj":"AB4","pred":"source","obj":"PubCasesORDO"},{"subj":"AB5","pred":"source","obj":"PubCasesORDO"},{"subj":"AB6","pred":"source","obj":"PubCasesORDO"},{"subj":"AB7","pred":"source","obj":"PubCasesORDO"},{"subj":"AB8","pred":"source","obj":"PubCasesORDO"},{"subj":"AB9","pred":"source","obj":"PubCasesORDO"},{"subj":"AB10","pred":"source","obj":"PubCasesORDO"},{"subj":"AB11","pred":"source","obj":"PubCasesORDO"},{"subj":"AB12","pred":"source","obj":"PubCasesORDO"},{"subj":"AB13","pred":"source","obj":"PubCasesORDO"},{"subj":"AB14","pred":"source","obj":"PubCasesORDO"}]},{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":240,"end":256},"obj":"http://purl.obolibrary.org/obo/UBERON_0000007"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":250,"end":256},"obj":"http://purl.obolibrary.org/obo/UBERON_0002530"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":1055,"end":1061},"obj":"http://purl.obolibrary.org/obo/UBERON_0002530"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":258,"end":266},"obj":"http://purl.obolibrary.org/obo/UBERON_0001264"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":1070,"end":1078},"obj":"http://purl.obolibrary.org/obo/UBERON_0001264"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":272,"end":280},"obj":"http://purl.obolibrary.org/obo/UBERON_0002114"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":1043,"end":1061},"obj":"http://purl.obolibrary.org/obo/UBERON_0001132"},{"id":"PD-UBERON-AE-B_T8","span":{"begin":1243,"end":1249},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T8","pred":"source","obj":"UBERON-AE"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":331,"end":335},"obj":"gene:4221"},{"id":"T1","span":{"begin":385,"end":398},"obj":"disease:C0206731"},{"id":"T2","span":{"begin":331,"end":335},"obj":"gene:4221"},{"id":"T3","span":{"begin":373,"end":380},"obj":"disease:C0023798"},{"id":"T4","span":{"begin":569,"end":573},"obj":"gene:4221"},{"id":"T5","span":{"begin":526,"end":546},"obj":"disease:C0241961"},{"id":"T6","span":{"begin":635,"end":639},"obj":"gene:4221"},{"id":"T7","span":{"begin":610,"end":631},"obj":"disease:C0206754"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#93ecab","default":true},{"id":"PubmedHPO","color":"#ec9394"},{"id":"DisGeNET5_gene_disease","color":"#93aeec"},{"id":"performance-test","color":"#c8ec93"},{"id":"PubCasesHPO","color":"#ec93e2"},{"id":"PubCasesORDO","color":"#93ecdb"},{"id":"UBERON-AE","color":"#ecc193"},{"id":"DisGeNET","color":"#a793ec"}]}]}}