PubMed:9935177 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/9935177","sourcedb":"PubMed","sourceid":"9935177","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9935177","text":"MEN1 gene mutation analysis of sporadic adrenocortical lesions.\nTo 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--\u003eA 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--\u003eA splice mutation in intron 4 might cause a variant of the MEN1 phenotype.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"9935177_0","span":{"begin":1123,"end":1128},"obj":"ProteinMutation"},{"id":"9935177_1","span":{"begin":1130,"end":1135},"obj":"ProteinMutation"},{"id":"9935177_2","span":{"begin":1137,"end":1142},"obj":"ProteinMutation"},{"id":"9935177_3","span":{"begin":1157,"end":1162},"obj":"ProteinMutation"}],"attributes":[{"id":"9935177_0_ProteinMutation","pred":"proteinmutation","subj":"9935177_0","obj":"rs61736636"},{"id":"9935177_1_ProteinMutation","pred":"proteinmutation","subj":"9935177_1","obj":"rs607969"},{"id":"9935177_2_ProteinMutation","pred":"proteinmutation","subj":"9935177_2","obj":"rs607969"},{"id":"9935177_3_ProteinMutation","pred":"proteinmutation","subj":"9935177_3","obj":"rs138770431"},{"subj":"9935177_0","pred":"source","obj":"PubTator4TogoVar"},{"subj":"9935177_1","pred":"source","obj":"PubTator4TogoVar"},{"subj":"9935177_2","pred":"source","obj":"PubTator4TogoVar"},{"subj":"9935177_3","pred":"source","obj":"PubTator4TogoVar"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":91,"end":95},"obj":"gene:4221"},{"id":"T1","span":{"begin":108,"end":121},"obj":"disease:C0596263"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"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"}]},{"project":"DisGeNET5_variant_disease","denotations":[{"id":"9935177-6#87#92#geners607969","span":{"begin":1137,"end":1142},"obj":"geners607969"},{"id":"9935177-6#158#180#diseaseC0206667","span":{"begin":1208,"end":1230},"obj":"diseaseC0206667"}],"relations":[{"id":"87#92#geners607969158#180#diseaseC0206667","pred":"associated_with","subj":"9935177-6#87#92#geners607969","obj":"9935177-6#158#180#diseaseC0206667"}],"attributes":[{"subj":"9935177-6#87#92#geners607969","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"9935177-6#158#180#diseaseC0206667","pred":"source","obj":"DisGeNET5_variant_disease"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"9935177-1#27#31#gene4221","span":{"begin":91,"end":95},"obj":"gene4221"},{"id":"9935177-1#44#57#diseaseC0596263","span":{"begin":108,"end":121},"obj":"diseaseC0596263"},{"id":"9935177-8#60#64#gene4221","span":{"begin":1515,"end":1519},"obj":"gene4221"},{"id":"9935177-8#89#113#diseaseC0206695","span":{"begin":1544,"end":1568},"obj":"diseaseC0206695"}],"relations":[{"id":"27#31#gene422144#57#diseaseC0596263","pred":"associated_with","subj":"9935177-1#27#31#gene4221","obj":"9935177-1#44#57#diseaseC0596263"},{"id":"60#64#gene422189#113#diseaseC0206695","pred":"associated_with","subj":"9935177-8#60#64#gene4221","obj":"9935177-8#89#113#diseaseC0206695"}],"attributes":[{"subj":"9935177-1#27#31#gene4221","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9935177-1#44#57#diseaseC0596263","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9935177-8#60#64#gene4221","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9935177-8#89#113#diseaseC0206695","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubTator4TogoVar","color":"#93c7ec","default":true},{"id":"DisGeNET","color":"#e1ec93"},{"id":"DisGeNET5_variant_disease","color":"#dd93ec"},{"id":"DisGeNET5_gene_disease","color":"#93ecc3"}]}]}}