{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:10:49Z","timestamp":1791943849365,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,3]]},"abstract":"Abstract<\/jats:title>\n \n Approximately 10% of gastrointestinal stromal tumors (GISTs) harbor reportedly no\n KIT<\/jats:italic>\n and\n PDGFRA<\/jats:italic>\n mutations (wild\u2010type GISTs). The clinicopathological features and oncologic outcomes of wild\u2010type GISTs based on molecular profiles are unknown. We recruited 35 wild\u2010type GIST patients from the two registry studies of high\u2010risk GISTs between 2012 and 2015 and primary GISTs between 2003 and 2014. Molecular profiling of wild\u2010type GISTs was performed by targeted next\u2010generation sequencing (NGS) using formalin\u2010fixed paraffin\u2010embedded tumor samples. Among 35 wild\u2010type GISTs, targeted NGS analysis detected\n NF1<\/jats:italic>\n ,\n SDH<\/jats:italic>\n , or\n BRAF<\/jats:italic>\n mutation: 16 NF1\u2010GISTs with various\n NF1<\/jats:italic>\n mutations, 12 SDH\u2010GISTs (4 with\n SDHA<\/jats:italic>\n mutations, 4 with\n SDHB<\/jats:italic>\n mutations, and 4 with SDHB\u2010negative staining), and 5 BRAF\u2010GISTs with the V600E mutation. Two GISTs showed no mutations based on our targeted NGS analysis. Additional gene mutations were infrequent in primary wild\u2010type GISTs and found in\n TP53<\/jats:italic>\n ,\n CREBBP<\/jats:italic>\n ,\n CDKN2A<\/jats:italic>\n , and\n CHEK2<\/jats:italic>\n . Most NF1\u2010GISTs were located in the small intestine (\n N<\/jats:italic>\n \u2009=\u200912; 75%) and showed spindle cell features (\n N<\/jats:italic>\n \u2009=\u200915; 94%) and multiple tumors (\n N<\/jats:italic>\n \u2009=\u20096, 38%) with modest proliferation activities. In contrast, SDH\u2010GISTs were predominantly found in the stomach (\n N<\/jats:italic>\n \u2009=\u200911; 92%), exhibiting epithelioid cell (\n N<\/jats:italic>\n \u2009=\u20096; 50%) and multiple (\n N<\/jats:italic>\n \u2009=\u20096, 50%) features. The overall survival of patients with SDH\u2010GISTs appeared to be better than that of BRAF\u2010GISTs (\n p<\/jats:italic>\n \u2009=\u20090.0107) or NF1\u2010GISTs (\n p<\/jats:italic>\n \u2009=\u20090.0754), respectively. In conclusion, major molecular changes in wild\u2010type GISTs include\n NF1<\/jats:italic>\n ,\n SDH<\/jats:italic>\n , and\n BRAF<\/jats:italic>\n . NF1\u2010GISTs involved multifocal spindle cell tumors in the small intestine. SDH\u2010GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.\n <\/jats:p>","DOI":"10.1111\/cas.16058","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T03:09:45Z","timestamp":1704424185000},"page":"894-904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Molecular and clinicopathological features of\n KIT<\/i>\n \/\n PDGFRA<\/i>\n wild\u2010type<\/scp>\n gastrointestinal stromal tumors"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-6317","authenticated-orcid":false,"given":"Toshirou","family":"Nishida","sequence":"first","affiliation":[{"name":"Department of Surgery Japan Community Health\u2010care Organization Osaka Hospital Osaka Japan"},{"name":"Department of Surgery National Cancer Center Hospital Tokyo Japan"},{"name":"National Institute of Biomedical Innovation, Health and Nutrition, Laboratory of Nuclear Transport Dynamics Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-9064","authenticated-orcid":false,"given":"Yoichi","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine National Cancer Center Hospital East Kashiwa Japan"},{"name":"Department of Experimental Therapeutics National Cancer Center Hospital East Kashiwa Japan"},{"name":"Department of Medical Oncology National Cancer Center Hospital East Kashiwa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2397-1478","authenticated-orcid":false,"given":"Tsuyoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Osaka University Graduate School of Medicine Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1733-5064","authenticated-orcid":false,"given":"Takuro","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Osaka University Graduate School of Medicine Suita Japan"},{"name":"Department of Surgery Osaka Police Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Hisamori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Manaka","sequence":"additional","affiliation":[{"name":"Department of Surgery Kyoto Katsura Hospital Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Surgery Saiseikai Kumamoto Hospital Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hyogo Medical University School of Medicine Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics National Cancer Center Research Institute Tokyo 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