PubMed:28270683 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28270683","sourcedb":"PubMed","sourceid":"28270683","text":"MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation.\nKIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs. MAX genomic inactivation is associated with p16 silencing in the absence of p16 coding sequence deletion and MAX induction restores p16 expression and inhibits GIST proliferation. Hence, MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs.","tracks":[{"project":"kaiyin_test","denotations":[{"id":"T2","span":{"begin":98,"end":101},"obj":"Gene"},{"id":"T3","span":{"begin":103,"end":109},"obj":"Gene"},{"id":"T4","span":{"begin":111,"end":114},"obj":"Gene"},{"id":"T1","span":{"begin":119,"end":122},"obj":"Gene"},{"id":"T5","span":{"begin":123,"end":132},"obj":"Var"},{"id":"T6","span":{"begin":166,"end":175},"obj":"Reg"},{"id":"T7","span":{"begin":191,"end":223},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T2","obj":"T5"},{"id":"R2","pred":"ThemeOf","subj":"T1","obj":"T5"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T5"},{"id":"R4","pred":"ThemeOf","subj":"T3","obj":"T5"},{"id":"R5","pred":"CauseOf","subj":"T5","obj":"T6"},{"id":"R6","pred":"ThemeOf","subj":"T7","obj":"T6"}],"attributes":[{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T1","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"},{"subj":"T7","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T2","span":{"begin":98,"end":101},"obj":"Gene"},{"id":"T3","span":{"begin":103,"end":109},"obj":"Gene"},{"id":"T4","span":{"begin":111,"end":114},"obj":"Gene"},{"id":"T1","span":{"begin":119,"end":122},"obj":"Gene"},{"id":"T5","span":{"begin":123,"end":132},"obj":"Var"},{"id":"T6","span":{"begin":166,"end":175},"obj":"Reg"},{"id":"T7","span":{"begin":191,"end":223},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T2","obj":"T5"},{"id":"R2","pred":"ThemeOf","subj":"T1","obj":"T5"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T5"},{"id":"R4","pred":"ThemeOf","subj":"T3","obj":"T5"},{"id":"R5","pred":"CauseOf","subj":"T5","obj":"T6"},{"id":"R6","pred":"ThemeOf","subj":"T7","obj":"T6"}],"attributes":[{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T1","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"},{"subj":"T7","pred":"source","obj":"name_no"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":111,"end":114},"obj":"Disease"},{"id":"T2","span":{"begin":176,"end":187},"obj":"Disease"},{"id":"T3","span":{"begin":386,"end":409},"obj":"Disease"},{"id":"T4","span":{"begin":583,"end":586},"obj":"Disease"},{"id":"T5","span":{"begin":692,"end":695},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0018975"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005043"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0016912"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0018975"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0018975"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T4","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"}]},{"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":0,"end":3},"obj":"GENE"},{"id":"T1","span":{"begin":4,"end":16},"obj":"NEGREG"},{"id":"T2","span":{"begin":23,"end":28},"obj":"REG"},{"id":"T3","span":{"begin":38,"end":42},"obj":"DISEASE"},{"id":"T4","span":{"begin":60,"end":69},"obj":"REG"},{"id":"T5","span":{"begin":70,"end":73},"obj":"GENE"},{"id":"T6","span":{"begin":78,"end":96},"obj":"CPA"},{"id":"T7","span":{"begin":98,"end":101},"obj":"GENE"},{"id":"T8","span":{"begin":103,"end":109},"obj":"GENE"},{"id":"T9","span":{"begin":111,"end":114},"obj":"GENE"},{"id":"T10","span":{"begin":119,"end":122},"obj":"GENE"},{"id":"T11","span":{"begin":123,"end":132},"obj":"VAR"},{"id":"T12","span":{"begin":147,"end":157},"obj":"REG"},{"id":"T13","span":{"begin":176,"end":187},"obj":"MPA"},{"id":"T14","span":{"begin":176,"end":223},"obj":"DISEASE"},{"id":"T15","span":{"begin":191,"end":223},"obj":"DISEASE"},{"id":"T16","span":{"begin":225,"end":230},"obj":"DISEASE"},{"id":"T17","span":{"begin":256,"end":267},"obj":"VAR"},{"id":"T18","span":{"begin":300,"end":310},"obj":"DISEASE"},{"id":"T19","span":{"begin":340,"end":350},"obj":"VAR"},{"id":"T20","span":{"begin":352,"end":364},"obj":"REG"},{"id":"T21","span":{"begin":426,"end":436},"obj":"VAR"},{"id":"T22","span":{"begin":451,"end":463},"obj":"NEGREG"},{"id":"T23","span":{"begin":464,"end":473},"obj":"VAR"},{"id":"T24","span":{"begin":496,"end":499},"obj":"GENE"},{"id":"T25","span":{"begin":517,"end":522},"obj":"DISEASE"},{"id":"T26","span":{"begin":538,"end":541},"obj":"GENE"},{"id":"T27","span":{"begin":542,"end":551},"obj":"VAR"},{"id":"T28","span":{"begin":583,"end":602},"obj":"DISEASE"},{"id":"T29","span":{"begin":583,"end":596},"obj":"DISEASE"},{"id":"T30","span":{"begin":630,"end":634},"obj":"NEGREG"},{"id":"T31","span":{"begin":638,"end":641},"obj":"GENE"},{"id":"T32","span":{"begin":650,"end":660},"obj":"MPA"},{"id":"T33","span":{"begin":692,"end":711},"obj":"DISEASE"},{"id":"T34","span":{"begin":692,"end":705},"obj":"DISEASE"},{"id":"T35","span":{"begin":749,"end":760},"obj":"DISEASE"},{"id":"T36","span":{"begin":785,"end":788},"obj":"GENE"},{"id":"T37","span":{"begin":797,"end":809},"obj":"NEGREG"},{"id":"T38","span":{"begin":829,"end":832},"obj":"GENE"},{"id":"T39","span":{"begin":833,"end":842},"obj":"NEGREG"},{"id":"T40","span":{"begin":861,"end":864},"obj":"GENE"},{"id":"T41","span":{"begin":881,"end":889},"obj":"VAR"},{"id":"T42","span":{"begin":894,"end":897},"obj":"GENE"},{"id":"T43","span":{"begin":898,"end":907},"obj":"POSREG"},{"id":"T44","span":{"begin":908,"end":916},"obj":"POSREG"},{"id":"T45","span":{"begin":917,"end":920},"obj":"GENE"},{"id":"T46","span":{"begin":921,"end":931},"obj":"MPA"},{"id":"T47","span":{"begin":936,"end":944},"obj":"NEGREG"},{"id":"T48","span":{"begin":950,"end":963},"obj":"CPA"},{"id":"T49","span":{"begin":972,"end":975},"obj":"GENE"},{"id":"T50","span":{"begin":976,"end":988},"obj":"NEGREG"},{"id":"T51","span":{"begin":994,"end":1000},"obj":"REG"},{"id":"T52","span":{"begin":1010,"end":1014},"obj":"DISEASE"},{"id":"T53","span":{"begin":1028,"end":1037},"obj":"POSREG"},{"id":"T54","span":{"begin":1038,"end":1048},"obj":"CPA"},{"id":"T55","span":{"begin":1049,"end":1057},"obj":"MPA"},{"id":"T56","span":{"begin":1067,"end":1072},"obj":"DISEASE"}],"relations":[{"id":"R25","pred":"ThemeOf","subj":"T16","obj":"T17"},{"id":"R26","pred":"CauseOf","subj":"T17","obj":"T12"},{"id":"R27","pred":"ThemeOf","subj":"T18","obj":"T12"},{"id":"R28","pred":"ThemeOf","subj":"T18","obj":"T17"},{"id":"R29","pred":"CauseOf","subj":"T19","obj":"T20"},{"id":"R30","pred":"CauseOf","subj":"T21","obj":"T22"},{"id":"R31","pred":"CauseOf","subj":"T23","obj":"T22"},{"id":"R32","pred":"ThemeOf","subj":"T24","obj":"T21"},{"id":"R33","pred":"ThemeOf","subj":"T24","obj":"T23"},{"id":"R34","pred":"ThemeOf","subj":"T25","obj":"T22"},{"id":"R35","pred":"ThemeOf","subj":"T26","obj":"T27"},{"id":"R36","pred":"CauseOf","subj":"T27","obj":"T30"},{"id":"R37","pred":"ThemeOf","subj":"T28","obj":"T30"},{"id":"R38","pred":"ThemeOf","subj":"T31","obj":"T32"},{"id":"R39","pred":"ThemeOf","subj":"T32","obj":"T30"},{"id":"R40","pred":"ThemeOf","subj":"T33","obj":"T30"},{"id":"R41","pred":"ThemeOf","subj":"T35","obj":"T30"},{"id":"R42","pred":"ThemeOf","subj":"T36","obj":"T37"},{"id":"R43","pred":"CauseOf","subj":"T37","obj":"T39"},{"id":"R44","pred":"CauseOf","subj":"T37","obj":"T47"},{"id":"R45","pred":"ThemeOf","subj":"T38","obj":"T39"},{"id":"R46","pred":"ThemeOf","subj":"T40","obj":"T41"},{"id":"R47","pred":"CauseOf","subj":"T41","obj":"T39"},{"id":"R48","pred":"CauseOf","subj":"T41","obj":"T44"},{"id":"R52","pred":"CauseOf","subj":"T43","obj":"T47"},{"id":"R53","pred":"ThemeOf","subj":"T46","obj":"T44"},{"id":"R54","pred":"ThemeOf","subj":"T48","obj":"T47"},{"id":"R55","pred":"ThemeOf","subj":"T49","obj":"T50"},{"id":"R56","pred":"CauseOf","subj":"T50","obj":"T51"},{"id":"R57","pred":"CauseOf","subj":"T50","obj":"T53"},{"id":"R58","pred":"ThemeOf","subj":"T52","obj":"T50"},{"id":"R59","pred":"ThemeOf","subj":"T52","obj":"T51"},{"id":"R60","pred":"ThemeOf","subj":"T52","obj":"T53"},{"id":"R61","pred":"ThemeOf","subj":"T54","obj":"T53"},{"id":"R62","pred":"ThemeOf","subj":"T54","obj":"T55"},{"id":"R63","pred":"ThemeOf","subj":"T55","obj":"T53"},{"id":"R64","pred":"ThemeOf","subj":"T56","obj":"T51"},{"id":"R65","pred":"ThemeOf","subj":"T56","obj":"T53"},{"id":"R66","pred":"ThemeOf","subj":"T56","obj":"T54"},{"id":"R67","pred":"ThemeOf","subj":"T56","obj":"T55"},{"id":"R0","pred":"ThemeOf","subj":"T0","obj":"T1"},{"id":"R1","pred":"ThemeOf","subj":"T0","obj":"T2"},{"id":"R2","pred":"CauseOf","subj":"T1","obj":"T2"},{"id":"R3","pred":"CauseOf","subj":"T1","obj":"T4"},{"id":"R4","pred":"ThemeOf","subj":"T3","obj":"T1"},{"id":"R5","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R6","pred":"ThemeOf","subj":"T3","obj":"T4"},{"id":"R7","pred":"ThemeOf","subj":"T6","obj":"T2"},{"id":"R8","pred":"ThemeOf","subj":"T6","obj":"T4"},{"id":"R9","pred":"ThemeOf","subj":"T7","obj":"T11"},{"id":"R10","pred":"ThemeOf","subj":"T7","obj":"T17"},{"id":"R11","pred":"ThemeOf","subj":"T8","obj":"T11"},{"id":"R12","pred":"ThemeOf","subj":"T8","obj":"T17"},{"id":"R13","pred":"ThemeOf","subj":"T9","obj":"T11"},{"id":"R14","pred":"ThemeOf","subj":"T9","obj":"T17"},{"id":"R15","pred":"ThemeOf","subj":"T10","obj":"T11"},{"id":"R16","pred":"ThemeOf","subj":"T10","obj":"T17"},{"id":"R17","pred":"CauseOf","subj":"T11","obj":"T12"},{"id":"R18","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R19","pred":"ThemeOf","subj":"T13","obj":"T17"},{"id":"R20","pred":"ThemeOf","subj":"T15","obj":"T12"},{"id":"R21","pred":"ThemeOf","subj":"T15","obj":"T13"},{"id":"R22","pred":"ThemeOf","subj":"T15","obj":"T17"},{"id":"R23","pred":"ThemeOf","subj":"T16","obj":"T12"},{"id":"R24","pred":"ThemeOf","subj":"T16","obj":"T13"},{"id":"R49","pred":"CauseOf","subj":"T41","obj":"T47"},{"id":"R50","pred":"ThemeOf","subj":"T42","obj":"T43"},{"id":"R51","pred":"CauseOf","subj":"T43","obj":"T44"}],"attributes":[{"subj":"T0","pred":"source","obj":"sonoma2"},{"subj":"T1","pred":"source","obj":"sonoma2"},{"subj":"T2","pred":"source","obj":"sonoma2"},{"subj":"T3","pred":"source","obj":"sonoma2"},{"subj":"T4","pred":"source","obj":"sonoma2"},{"subj":"T5","pred":"source","obj":"sonoma2"},{"subj":"T6","pred":"source","obj":"sonoma2"},{"subj":"T7","pred":"source","obj":"sonoma2"},{"subj":"T8","pred":"source","obj":"sonoma2"},{"subj":"T9","pred":"source","obj":"sonoma2"},{"subj":"T10","pred":"source","obj":"sonoma2"},{"subj":"T11","pred":"source","obj":"sonoma2"},{"subj":"T12","pred":"source","obj":"sonoma2"},{"subj":"T13","pred":"source","obj":"sonoma2"},{"subj":"T14","pred":"source","obj":"sonoma2"},{"subj":"T15","pred":"source","obj":"sonoma2"},{"subj":"T16","pred":"source","obj":"sonoma2"},{"subj":"T17","pred":"source","obj":"sonoma2"},{"subj":"T18","pred":"source","obj":"sonoma2"},{"subj":"T19","pred":"source","obj":"sonoma2"},{"subj":"T20","pred":"source","obj":"sonoma2"},{"subj":"T21","pred":"source","obj":"sonoma2"},{"subj":"T22","pred":"source","obj":"sonoma2"},{"subj":"T23","pred":"source","obj":"sonoma2"},{"subj":"T24","pred":"source","obj":"sonoma2"},{"subj":"T25","pred":"source","obj":"sonoma2"},{"subj":"T26","pred":"source","obj":"sonoma2"},{"subj":"T27","pred":"source","obj":"sonoma2"},{"subj":"T28","pred":"source","obj":"sonoma2"},{"subj":"T29","pred":"source","obj":"sonoma2"},{"subj":"T30","pred":"source","obj":"sonoma2"},{"subj":"T31","pred":"source","obj":"sonoma2"},{"subj":"T32","pred":"source","obj":"sonoma2"},{"subj":"T33","pred":"source","obj":"sonoma2"},{"subj":"T34","pred":"source","obj":"sonoma2"},{"subj":"T35","pred":"source","obj":"sonoma2"},{"subj":"T36","pred":"source","obj":"sonoma2"},{"subj":"T37","pred":"source","obj":"sonoma2"},{"subj":"T38","pred":"source","obj":"sonoma2"},{"subj":"T39","pred":"source","obj":"sonoma2"},{"subj":"T40","pred":"source","obj":"sonoma2"},{"subj":"T41","pred":"source","obj":"sonoma2"},{"subj":"T42","pred":"source","obj":"sonoma2"},{"subj":"T43","pred":"source","obj":"sonoma2"},{"subj":"T44","pred":"source","obj":"sonoma2"},{"subj":"T45","pred":"source","obj":"sonoma2"},{"subj":"T46","pred":"source","obj":"sonoma2"},{"subj":"T47","pred":"source","obj":"sonoma2"},{"subj":"T48","pred":"source","obj":"sonoma2"},{"subj":"T49","pred":"source","obj":"sonoma2"},{"subj":"T50","pred":"source","obj":"sonoma2"},{"subj":"T51","pred":"source","obj":"sonoma2"},{"subj":"T52","pred":"source","obj":"sonoma2"},{"subj":"T53","pred":"source","obj":"sonoma2"},{"subj":"T54","pred":"source","obj":"sonoma2"},{"subj":"T55","pred":"source","obj":"sonoma2"},{"subj":"T56","pred":"source","obj":"sonoma2"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":386,"end":396},"obj":"Body_part"},{"id":"T2","span":{"begin":481,"end":491},"obj":"Body_part"},{"id":"T3","span":{"begin":1038,"end":1048},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005694"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/GO_0005694"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_2000098"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":38,"end":42},"obj":"Phenotype"},{"id":"T2","span":{"begin":191,"end":223},"obj":"Phenotype"},{"id":"T3","span":{"begin":225,"end":230},"obj":"Phenotype"},{"id":"T4","span":{"begin":376,"end":381},"obj":"Phenotype"},{"id":"T5","span":{"begin":517,"end":522},"obj":"Phenotype"},{"id":"T6","span":{"begin":597,"end":602},"obj":"Phenotype"},{"id":"T7","span":{"begin":706,"end":711},"obj":"Phenotype"},{"id":"T8","span":{"begin":755,"end":760},"obj":"Phenotype"},{"id":"T9","span":{"begin":778,"end":783},"obj":"Phenotype"},{"id":"T10","span":{"begin":945,"end":949},"obj":"Phenotype"},{"id":"T11","span":{"begin":1010,"end":1014},"obj":"Phenotype"},{"id":"T12","span":{"begin":1067,"end":1072},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0100723"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0100723"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0100723"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0100723"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0100723"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"HP:0100723"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"HP:0100723"},{"id":"A8","pred":"hp_id","subj":"T8","obj":"HP:0100723"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"HP:0100723"},{"id":"A10","pred":"hp_id","subj":"T10","obj":"HP:0100723"},{"id":"A11","pred":"hp_id","subj":"T11","obj":"HP:0100723"},{"id":"A12","pred":"hp_id","subj":"T12","obj":"HP:0100723"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"},{"subj":"T3","pred":"source","obj":"HP-phenotype"},{"subj":"T4","pred":"source","obj":"HP-phenotype"},{"subj":"T5","pred":"source","obj":"HP-phenotype"},{"subj":"T6","pred":"source","obj":"HP-phenotype"},{"subj":"T7","pred":"source","obj":"HP-phenotype"},{"subj":"T8","pred":"source","obj":"HP-phenotype"},{"subj":"T9","pred":"source","obj":"HP-phenotype"},{"subj":"T10","pred":"source","obj":"HP-phenotype"},{"subj":"T11","pred":"source","obj":"HP-phenotype"},{"subj":"T12","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"kaiyin_test","color":"#e2ec93","default":true},{"id":"name_no","color":"#dc93ec"},{"id":"mondo_disease","color":"#93ecc2"},{"id":"sonoma2","color":"#eca893"},{"id":"Anatomy-UBERON","color":"#9398ec"},{"id":"HP-phenotype","color":"#b2ec93"}]}]}}