PubMed:10076565 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":38,"end":60},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":132,"end":153},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":227,"end":249},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":1645,"end":1667},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0002447"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0002447"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0002447"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0002447"}],"text":"Mutations of the beta-catenin gene in endometrial carcinomas.\nTo investigate the contribution of beta-catenin to the development of endometrial carcinoma, we searched for genetic alterations of the beta-catenin gene in primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential GSK-3 beta phosphorylation sites. Each of the mutations resulted in the substitution of serine/threonine residues that have been implicated in the down-regulation of beta-catenin through phosphorylation by GSK-3 beta kinase. Furthermore, the incidence of beta-catenin mutations was significantly higher in early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014, Fisher's exact test). Replication error (RER)-positive phenotype was not detected in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed RER. We performed immunohistochemistry of beta-catenin in 17 cases for which tissue samples were available. We confirmed accumulation of beta-catenin protein in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid alterations had occurred at codon 33 and 37. The other case had no mutation in exon 3. Our results suggested that mutations at serine/threonine residues involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin. Accumulation of mutant beta-catenin could contribute to the development of a subset of endometrial carcinomas, particularly those of the early-onset type."}

{"project":"PennBioIE","denotations":[{"id":"T1","span":{"begin":17,"end":29},"obj":"protein"},{"id":"T2","span":{"begin":97,"end":109},"obj":"protein"},{"id":"T3","span":{"begin":198,"end":210},"obj":"protein"},{"id":"T4","span":{"begin":274,"end":280},"obj":"protein"},{"id":"T5","span":{"begin":288,"end":300},"obj":"protein"},{"id":"T6","span":{"begin":320,"end":326},"obj":"protein"},{"id":"T7","span":{"begin":327,"end":336},"obj":"protein"},{"id":"T8","span":{"begin":350,"end":360},"obj":"protein"},{"id":"T9","span":{"begin":483,"end":492},"obj":"protein"},{"id":"T10","span":{"begin":494,"end":495},"obj":"protein"},{"id":"T11","span":{"begin":495,"end":497},"obj":"protein"},{"id":"T12","span":{"begin":497,"end":498},"obj":"protein"},{"id":"T13","span":{"begin":500,"end":501},"obj":"protein"},{"id":"T14","span":{"begin":501,"end":503},"obj":"protein"},{"id":"T15","span":{"begin":503,"end":504},"obj":"protein"},{"id":"T16","span":{"begin":506,"end":507},"obj":"protein"},{"id":"T17","span":{"begin":507,"end":509},"obj":"protein"},{"id":"T18","span":{"begin":509,"end":510},"obj":"protein"},{"id":"T19","span":{"begin":512,"end":513},"obj":"protein"},{"id":"T20","span":{"begin":513,"end":515},"obj":"protein"},{"id":"T21","span":{"begin":515,"end":516},"obj":"protein"},{"id":"T22","span":{"begin":541,"end":551},"obj":"protein"},{"id":"T23","span":{"begin":587,"end":596},"obj":"protein"},{"id":"T24","span":{"begin":613,"end":625},"obj":"protein"},{"id":"T25","span":{"begin":629,"end":635},"obj":"protein"},{"id":"T26","span":{"begin":636,"end":645},"obj":"protein"},{"id":"T27","span":{"begin":707,"end":719},"obj":"protein"},{"id":"T28","span":{"begin":747,"end":764},"obj":"protein"},{"id":"T29","span":{"begin":796,"end":808},"obj":"protein"},{"id":"T30","span":{"begin":1022,"end":1034},"obj":"protein"},{"id":"T31","span":{"begin":1126,"end":1138},"obj":"protein"},{"id":"T32","span":{"begin":1221,"end":1233},"obj":"protein"},{"id":"T33","span":{"begin":1312,"end":1334},"obj":"protein"},{"id":"T34","span":{"begin":1351,"end":1356},"obj":"protein"},{"id":"T35","span":{"begin":1364,"end":1366},"obj":"protein"},{"id":"T36","span":{"begin":1390,"end":1398},"obj":"protein"},{"id":"T37","span":{"begin":1402,"end":1408},"obj":"protein"},{"id":"T38","span":{"begin":1437,"end":1446},"obj":"protein"},{"id":"T39","span":{"begin":1450,"end":1456},"obj":"protein"},{"id":"T40","span":{"begin":1457,"end":1466},"obj":"protein"},{"id":"T41","span":{"begin":1507,"end":1517},"obj":"protein"},{"id":"T42","span":{"begin":1544,"end":1556},"obj":"protein"},{"id":"T43","span":{"begin":1581,"end":1593},"obj":"protein"}],"text":"Mutations of the beta-catenin gene in endometrial carcinomas.\nTo investigate the contribution of beta-catenin to the development of endometrial carcinoma, we searched for genetic alterations of the beta-catenin gene in primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential GSK-3 beta phosphorylation sites. Each of the mutations resulted in the substitution of serine/threonine residues that have been implicated in the down-regulation of beta-catenin through phosphorylation by GSK-3 beta kinase. Furthermore, the incidence of beta-catenin mutations was significantly higher in early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014, Fisher's exact test). Replication error (RER)-positive phenotype was not detected in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed RER. We performed immunohistochemistry of beta-catenin in 17 cases for which tissue samples were available. We confirmed accumulation of beta-catenin protein in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid alterations had occurred at codon 33 and 37. The other case had no mutation in exon 3. Our results suggested that mutations at serine/threonine residues involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin. Accumulation of mutant beta-catenin could contribute to the development of a subset of endometrial carcinomas, particularly those of the early-onset type."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":17,"end":29},"obj":"gene:1499"},{"id":"T1","span":{"begin":38,"end":60},"obj":"disease:C0476089"},{"id":"T2","span":{"begin":198,"end":210},"obj":"gene:1499"},{"id":"T3","span":{"begin":227,"end":249},"obj":"disease:C0476089"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Mutations of the beta-catenin gene in endometrial carcinomas.\nTo investigate the contribution of beta-catenin to the development of endometrial carcinoma, we searched for genetic alterations of the beta-catenin gene in primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential GSK-3 beta phosphorylation sites. Each of the mutations resulted in the substitution of serine/threonine residues that have been implicated in the down-regulation of beta-catenin through phosphorylation by GSK-3 beta kinase. Furthermore, the incidence of beta-catenin mutations was significantly higher in early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014, Fisher's exact test). Replication error (RER)-positive phenotype was not detected in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed RER. We performed immunohistochemistry of beta-catenin in 17 cases for which tissue samples were available. We confirmed accumulation of beta-catenin protein in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid alterations had occurred at codon 33 and 37. The other case had no mutation in exon 3. Our results suggested that mutations at serine/threonine residues involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin. Accumulation of mutant beta-catenin could contribute to the development of a subset of endometrial carcinomas, particularly those of the early-onset type."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":132,"end":153},"obj":"HP_0012114"},{"id":"T2","span":{"begin":227,"end":249},"obj":"HP_0012114"},{"id":"T3","span":{"begin":399,"end":405},"obj":"HP_0002664"},{"id":"T4","span":{"begin":454,"end":460},"obj":"HP_0002664"},{"id":"T5","span":{"begin":892,"end":898},"obj":"HP_0002664"},{"id":"T6","span":{"begin":1006,"end":1012},"obj":"HP_0002664"},{"id":"T7","span":{"begin":1068,"end":1074},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1281,"end":1287},"obj":"HP_0002664"},{"id":"T9","span":{"begin":1645,"end":1667},"obj":"HP_0012114"}],"text":"Mutations of the beta-catenin gene in endometrial carcinomas.\nTo investigate the contribution of beta-catenin to the development of endometrial carcinoma, we searched for genetic alterations of the beta-catenin gene in primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential GSK-3 beta phosphorylation sites. Each of the mutations resulted in the substitution of serine/threonine residues that have been implicated in the down-regulation of beta-catenin through phosphorylation by GSK-3 beta kinase. Furthermore, the incidence of beta-catenin mutations was significantly higher in early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014, Fisher's exact test). Replication error (RER)-positive phenotype was not detected in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed RER. We performed immunohistochemistry of beta-catenin in 17 cases for which tissue samples were available. We confirmed accumulation of beta-catenin protein in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid alterations had occurred at codon 33 and 37. The other case had no mutation in exon 3. Our results suggested that mutations at serine/threonine residues involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin. Accumulation of mutant beta-catenin could contribute to the development of a subset of endometrial carcinomas, particularly those of the early-onset type."}