PubMed:10192393 JSONTXT

{"project":"PennBioIE","denotations":[{"id":"T1","span":{"begin":64,"end":76},"obj":"protein"},{"id":"T2","span":{"begin":78,"end":81},"obj":"protein"},{"id":"T3","span":{"begin":184,"end":196},"obj":"protein"},{"id":"T4","span":{"begin":209,"end":215},"obj":"protein"},{"id":"T5","span":{"begin":297,"end":300},"obj":"protein"},{"id":"T6","span":{"begin":301,"end":304},"obj":"protein"},{"id":"T7","span":{"begin":341,"end":353},"obj":"protein"},{"id":"T8","span":{"begin":354,"end":357},"obj":"protein"},{"id":"T9","span":{"begin":366,"end":371},"obj":"protein"},{"id":"T10","span":{"begin":419,"end":422},"obj":"protein"},{"id":"T11","span":{"begin":539,"end":565},"obj":"protein"},{"id":"T12","span":{"begin":567,"end":570},"obj":"protein"},{"id":"T13","span":{"begin":596,"end":605},"obj":"protein"},{"id":"T14","span":{"begin":630,"end":642},"obj":"protein"},{"id":"T15","span":{"begin":707,"end":719},"obj":"protein"},{"id":"T16","span":{"begin":812,"end":824},"obj":"protein"},{"id":"T17","span":{"begin":1106,"end":1118},"obj":"protein"},{"id":"T18","span":{"begin":1240,"end":1245},"obj":"protein"},{"id":"T19","span":{"begin":1497,"end":1506},"obj":"protein"},{"id":"T20","span":{"begin":1563,"end":1569},"obj":"protein"},{"id":"T21","span":{"begin":1666,"end":1678},"obj":"protein"},{"id":"T22","span":{"begin":1679,"end":1682},"obj":"protein"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10192393-10#19#25#gene1499","span":{"begin":1563,"end":1569},"obj":"gene1499"},{"id":"10192393-10#192#205#diseaseC0596263","span":{"begin":1736,"end":1749},"obj":"diseaseC0596263"},{"id":"10192393-8#17#22#gene51176","span":{"begin":1240,"end":1245},"obj":"gene51176"},{"id":"10192393-8#89#103#diseaseC0206711","span":{"begin":1312,"end":1326},"obj":"diseaseC0206711"}],"relations":[{"id":"19#25#gene1499192#205#diseaseC0596263","pred":"associated_with","subj":"10192393-10#19#25#gene1499","obj":"10192393-10#192#205#diseaseC0596263"},{"id":"17#22#gene5117689#103#diseaseC0206711","pred":"associated_with","subj":"10192393-8#17#22#gene51176","obj":"10192393-8#89#103#diseaseC0206711"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBIDiseaseCorpus","denotations":[{"id":"T1","span":{"begin":15,"end":26},"obj":"DiseaseClass:D012878"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass:D009369"},{"id":"T3","span":{"begin":483,"end":496},"obj":"DiseaseClass:D003110"},{"id":"T4","span":{"begin":539,"end":565},"obj":"SpecificDisease:D011125"},{"id":"T5","span":{"begin":567,"end":570},"obj":"SpecificDisease:D011125"},{"id":"T6","span":{"begin":670,"end":698},"obj":"CompositeMention:D003110|D009369"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass:D012878"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease:D018296"},{"id":"T9","span":{"begin":1021,"end":1035},"obj":"SpecificDisease:D018296"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"DiseaseClass:D012878"},{"id":"T11","span":{"begin":1262,"end":1268},"obj":"Modifier:D009369"},{"id":"T12","span":{"begin":1312,"end":1326},"obj":"SpecificDisease:D018296"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"DiseaseClass:D009369"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"DiseaseClass:D009369"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1563,"end":1569},"obj":"gene:1499"},{"id":"T1","span":{"begin":1736,"end":1749},"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/"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":443,"end":449},"obj":"HP_0002664"},{"id":"T2","span":{"begin":483,"end":496},"obj":"HP_0003003"},{"id":"T3","span":{"begin":483,"end":496},"obj":"HP_0100273"},{"id":"T4","span":{"begin":489,"end":496},"obj":"HP_0002664"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"HP_0002664"},{"id":"T5","span":{"begin":670,"end":698},"obj":"HP_0003003"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"HP_0002664"},{"id":"T6","span":{"begin":670,"end":698},"obj":"HP_0100273"},{"id":"T7","span":{"begin":691,"end":698},"obj":"HP_0002664"},{"id":"T8","span":{"begin":855,"end":867},"obj":"HP_0008069"},{"id":"T9","span":{"begin":860,"end":867},"obj":"HP_0002664"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"HP_0008069"},{"id":"T11","span":{"begin":1215,"end":1221},"obj":"HP_0002664"},{"id":"T12","span":{"begin":1262,"end":1268},"obj":"HP_0002664"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"testtesttest","denotations":[{"id":"T1","span":{"begin":15,"end":26},"obj":"DiseaseClass:D012878"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass:D009369"},{"id":"T3","span":{"begin":483,"end":496},"obj":"DiseaseClass:D003110"},{"id":"T4","span":{"begin":539,"end":565},"obj":"SpecificDisease:D011125"},{"id":"T5","span":{"begin":567,"end":570},"obj":"SpecificDisease:D011125"},{"id":"T6","span":{"begin":670,"end":698},"obj":"CompositeMention:D003110|D009369"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass:D012878"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease:D018296"},{"id":"T9","span":{"begin":1021,"end":1035},"obj":"SpecificDisease:D018296"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"DiseaseClass:D012878"},{"id":"T11","span":{"begin":1262,"end":1268},"obj":"Modifier:D009369"},{"id":"T12","span":{"begin":1312,"end":1326},"obj":"SpecificDisease:D018296"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"DiseaseClass:D009369"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"DiseaseClass:D009369"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Train","denotations":[{"id":"T1","span":{"begin":15,"end":26},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":483,"end":496},"obj":"DiseaseClass"},{"id":"T4","span":{"begin":539,"end":565},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":567,"end":570},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":670,"end":698},"obj":"CompositeMention"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"DiseaseClass"},{"id":"T11","span":{"begin":1262,"end":1268},"obj":"Modifier"},{"id":"T12","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"DiseaseClass"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"DiseaseClass"}],"attributes":[{"id":"A1","pred":"database_id","subj":"T1","obj":"D012878"},{"id":"A2","pred":"database_id","subj":"T2","obj":"D009369"},{"id":"A3","pred":"database_id","subj":"T3","obj":"D003110"},{"id":"A4","pred":"database_id","subj":"T4","obj":"D011125"},{"id":"A5","pred":"database_id","subj":"T5","obj":"D011125"},{"id":"A6","pred":"database_id","subj":"T6","obj":"D003110|D009369"},{"id":"A7","pred":"database_id","subj":"T7","obj":"D012878"},{"id":"A8","pred":"database_id","subj":"T8","obj":"D018296"},{"id":"A9","pred":"database_id","subj":"T9","obj":"D018296"},{"id":"A10","pred":"database_id","subj":"T10","obj":"D012878"},{"id":"A11","pred":"database_id","subj":"T11","obj":"D009369"},{"id":"A12","pred":"database_id","subj":"T12","obj":"D018296"},{"id":"A13","pred":"database_id","subj":"T13","obj":"D009369"},{"id":"A14","pred":"database_id","subj":"T14","obj":"D009369"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Corpus-All","denotations":[{"id":"T1","span":{"begin":15,"end":26},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":483,"end":496},"obj":"DiseaseClass"},{"id":"T4","span":{"begin":539,"end":565},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":567,"end":570},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":670,"end":698},"obj":"CompositeMention"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"DiseaseClass"},{"id":"T11","span":{"begin":1262,"end":1268},"obj":"Modifier"},{"id":"T12","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"DiseaseClass"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"DiseaseClass"}],"attributes":[{"id":"A1","pred":"database_id","subj":"T1","obj":"D012878"},{"id":"A2","pred":"database_id","subj":"T2","obj":"D009369"},{"id":"A3","pred":"database_id","subj":"T3","obj":"D003110"},{"id":"A4","pred":"database_id","subj":"T4","obj":"D011125"},{"id":"A5","pred":"database_id","subj":"T5","obj":"D011125"},{"id":"A6","pred":"database_id","subj":"T6","obj":"D003110|D009369"},{"id":"A7","pred":"database_id","subj":"T7","obj":"D012878"},{"id":"A8","pred":"database_id","subj":"T8","obj":"D018296"},{"id":"A9","pred":"database_id","subj":"T9","obj":"D018296"},{"id":"A10","pred":"database_id","subj":"T10","obj":"D012878"},{"id":"A11","pred":"database_id","subj":"T11","obj":"D009369"},{"id":"A12","pred":"database_id","subj":"T12","obj":"D018296"},{"id":"A13","pred":"database_id","subj":"T13","obj":"D009369"},{"id":"A14","pred":"database_id","subj":"T14","obj":"D009369"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Corpus-2stage-All","denotations":[{"id":"T1","span":{"begin":20,"end":26},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":471,"end":476},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":483,"end":496},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":670,"end":675},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":691,"end":698},"obj":"DiseaseClass"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":910,"end":914},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T11","span":{"begin":1210,"end":1221},"obj":"DiseaseClass"},{"id":"T12","span":{"begin":1262,"end":1268},"obj":"DiseaseClass"},{"id":"T13","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T14","span":{"begin":1385,"end":1392},"obj":"DiseaseClass"},{"id":"T15","span":{"begin":1615,"end":1622},"obj":"DiseaseClass"},{"id":"T16","span":{"begin":1736,"end":1749},"obj":"DiseaseClass"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Corpus-rezarta-All","denotations":[{"id":"T1","span":{"begin":20,"end":26},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":471,"end":476},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":483,"end":496},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":670,"end":675},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":691,"end":698},"obj":"DiseaseClass"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":910,"end":914},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T11","span":{"begin":1210,"end":1221},"obj":"DiseaseClass"},{"id":"T12","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T13","span":{"begin":1385,"end":1392},"obj":"DiseaseClass"},{"id":"T14","span":{"begin":1615,"end":1622},"obj":"DiseaseClass"},{"id":"T15","span":{"begin":1736,"end":1749},"obj":"DiseaseClass"},{"id":"T16","span":{"begin":1753,"end":1759},"obj":"Modifier"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Corpus-4oGuideline-All","denotations":[{"id":"T1","span":{"begin":15,"end":26},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":483,"end":496},"obj":"Modifier"},{"id":"T4","span":{"begin":691,"end":698},"obj":"DiseaseClass"},{"id":"T5","span":{"begin":855,"end":867},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T8","span":{"begin":1210,"end":1221},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1385,"end":1392},"obj":"SpecificDisease"},{"id":"T11","span":{"begin":1609,"end":1622},"obj":"SpecificDisease"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}

{"project":"NCBI-Disease-Corpus-Simple-All","denotations":[{"id":"T1","span":{"begin":20,"end":26},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":443,"end":449},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":471,"end":476},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":483,"end":496},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":670,"end":675},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":691,"end":698},"obj":"DiseaseClass"},{"id":"T7","span":{"begin":855,"end":867},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":879,"end":893},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":1021,"end":1035},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":1210,"end":1221},"obj":"DiseaseClass"},{"id":"T11","span":{"begin":1312,"end":1326},"obj":"SpecificDisease"},{"id":"T12","span":{"begin":1385,"end":1392},"obj":"DiseaseClass"},{"id":"T13","span":{"begin":1615,"end":1622},"obj":"DiseaseClass"},{"id":"T14","span":{"begin":1736,"end":1749},"obj":"DiseaseClass"}],"text":"A common human skin tumour is caused by activating mutations in beta-catenin.\nWNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans."}