{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:12:45Z","timestamp":1789841565869,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gastrointestinal stromal tumors (GIST) lacking mutations in KIT\/PDGFRA or RAS pathways and retaining an intact SDH complex are usually referred to as KIT\/PDGFRA\/SDH\/RAS\u2010P WT GIST or more simply <jats:italic>quadruple<\/jats:italic> WT GIST (~5% of all GIST). Despite efforts made, no recurrent genetic event in <jats:italic>quadruple<\/jats:italic> WT GIST has been identified so far. To further investigate this disease, we performed high throughput copy number analysis on <jats:italic>quadruple<\/jats:italic> WT GIST specimens identifying a recurrent focal gain in band 11q13.3 (involving <jats:italic>FGF3\/FGF4<\/jats:italic>) in 6\/8 cases. This event was not found in the other molecular GIST subgroups. <jats:italic>FGF3\/FGF4<\/jats:italic> duplication was associated with high expression of FGF4, both at mRNA and protein level, a growth factor normally not expressed in adult tissues or in KIT\/PDGFRA\u2010mutated GIST. FGFR1 was found to be the predominant FGF receptor expressed and phosphorylation of AKT was detected, suggesting that a FGF4\u2010FGFR1 autocrine loop could stimulate downstream signaling in <jats:italic>quadruple<\/jats:italic> WT GIST. Together with the recent reports of <jats:italic>quadruple<\/jats:italic> WT cases carrying FGFR1 activating alterations, these findings strengthen the hypothesis of a potential involvement of FGFR pathway deregulation in <jats:italic>quadruple<\/jats:italic> WT GIST, which may represent a rationale for novel therapeutic approaches.<\/jats:p>","DOI":"10.1002\/gcc.22753","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T01:09:55Z","timestamp":1553044195000},"page":"636-642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gain of FGF4 is a frequent event in KIT\/PDGFRA\/SDH\/RAS\u2010P WT GIST"],"prefix":"10.1002","volume":"58","author":[{"given":"Milena","family":"Urbini","sequence":"first","affiliation":[{"name":"\"Giorgio Prodi\" Cancer Research Center University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Indio","sequence":"additional","affiliation":[{"name":"\"Giorgio Prodi\" Cancer Research Center University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tarantino","sequence":"additional","affiliation":[{"name":"\"Giorgio Prodi\" Cancer Research Center University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Ravegnini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology FaBit; University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Angelini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology FaBit; University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Nannini","sequence":"additional","affiliation":[{"name":"Department of Specialized, Experimental and Diagnostic Medicine S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maristella","family":"Saponara","sequence":"additional","affiliation":[{"name":"Department of Specialized, Experimental and Diagnostic Medicine S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Santini","sequence":"additional","affiliation":[{"name":"Pathology Unit S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Pathology Unit S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Laboratory of Oncological and Transplant Molecular Pathology\u2014Pathology Unit S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 2, Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo Giovanni","family":"Casali","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 2, Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Grignani","sequence":"additional","affiliation":[{"name":"Sarcoma Unit Candiolo Cancer Institute \u2010 FPO  IRCCS Candiolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pession","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ardizzoni","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology S.Orsola\u2010Malpighi Hospital  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-0747","authenticated-orcid":false,"given":"Annalisa","family":"Astolfi","sequence":"additional","affiliation":[{"name":"\"Giorgio Prodi\" Cancer Research Center University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Abbondanza","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Department of Specialized, Experimental and Diagnostic Medicine S.Orsola\u2010Malpighi Hospital, University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.140"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182260752"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181d6150d"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0256"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.07.029"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000176433.81079.bd"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0152"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.325"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-685"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-16-0376"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-1075-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1872-y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1212-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14674"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.110"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-1037"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21699"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90331-X"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.11.3997"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.122"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25956"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12187"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1481"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_8_26_1","first-page":"5505","article-title":"High incidence of coamplification of hst\u20101 and int\u20102 genes in human esophageal carcinomas","volume":"49","author":"Tsuda T","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-011-1817-3"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3252"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.6.7934"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-12-0652"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0573-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.290"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0573"},{"key":"e_1_2_8_34_1","article-title":"A phase Ib study of BGJ398, a pan\u2010FGFR kinase inhibitor in combination with imatinib in patients with advanced gastrointestinal stromal tumor","author":"Kelly CM","year":"2018","journal-title":"Invest New Drugs"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22753","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22753","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.22753","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:19:26Z","timestamp":1694279966000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,16]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/gcc.22753"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22753","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,16]]},"assertion":[{"value":"2018-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}