{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:58:29Z","timestamp":1785466709079,"version":"3.56.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012330","name":"Okayama University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012330","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin J Gastroenterol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neurofibromatosis type 1 (NF1)-associated gastrointestinal stromal tumor (GIST) is a distinct subtype of wild-type GIST driven by loss of neurofibromin function rather than\n                    <jats:italic>KIT<\/jats:italic>\n                    or\n                    <jats:italic>PDGFRA<\/jats:italic>\n                    mutations. Although most NF1-associated GISTs exhibit relatively indolent behavior, a subset demonstrates aggressive progression, and the molecular mechanisms underlying this malignant transformation remain unclear. Here, we report a rare case of NF1-associated gastric GIST with polycomb repressive complex 2 (PRC2)-related epigenetic alteration. A 64-year-old man with NF1 was found to have a small submucosal gastric lesion on screening endoscopy. The tumor enlarged rapidly, and laparoscopic local resection was performed. Histopathological examination confirmed a high-risk gastric GIST with positivity for c-\n                    <jats:italic>KIT<\/jats:italic>\n                    , DOG-1, and CD34. Immunohistochemistry demonstrated preserved SDHB expression but complete loss of H3K27me3. Comprehensive genomic profiling revealed\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    loss,\n                    <jats:italic>CDKN2B<\/jats:italic>\n                    loss,\n                    <jats:italic>EED<\/jats:italic>\n                    loss, and\n                    <jats:italic>MYC<\/jats:italic>\n                    amplification, without pathogenic mutations in\n                    <jats:italic>KIT<\/jats:italic>\n                    or\n                    <jats:italic>PDGFRA<\/jats:italic>\n                    . Despite surgery and tyrosine kinase inhibitor therapy, the tumor rapidly progressed with peritoneal dissemination and malignant pleural effusion, and the patient died 17 months after surgery. This case highlights a possible association between secondary genomic alterations, PRC2-related epigenetic alteration, and aggressive tumor behavior in NF1-associated GIST. Integrated genomic and epigenomic evaluations may provide important insights into tumor behavior and therapeutic strategies for this rare GIST subtype.\n                  <\/jats:p>","DOI":"10.1007\/s12328-026-02362-9","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:31:55Z","timestamp":1779517915000},"page":"770-775","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurofibromatosis type 1\u2013associated gastric gastrointestinal stromal tumor with PRC2 loss"],"prefix":"10.1007","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-5754","authenticated-orcid":false,"given":"Masaya","family":"Iwamuro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy Hung","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Aya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyasu","family":"Kono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"2362_CR1","doi-asserted-by":"publisher","first-page":"3813","DOI":"10.1200\/JCO.2004.05.140","volume":"22","author":"CL Corless","year":"2004","unstructured":"Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004;22:3813\u201325.","journal-title":"J Clin Oncol"},{"key":"2362_CR2","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1200\/JCO.2003.04.190","volume":"21","author":"MC Heinrich","year":"2003","unstructured":"Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342\u20139.","journal-title":"J Clin Oncol"},{"key":"2362_CR3","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/01.pas.0000176433.81079.bd","volume":"30","author":"M Miettinen","year":"2006","unstructured":"Miettinen M, Fetsch JF, Sobin LH, et al. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 2006;30:90\u20136.","journal-title":"Am J Surg Pathol"},{"key":"2362_CR4","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1001\/jamaoncol.2016.0256","volume":"2","author":"SA Boikos","year":"2016","unstructured":"Boikos SA, Pappo AS, Killian JK, et al. Molecular Subtypes of KIT\/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic. JAMA Oncol. 2016;2:922\u20138.","journal-title":"JAMA Oncol"},{"key":"2362_CR5","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1186\/1471-2407-14-685","volume":"14","author":"M Nannini","year":"2014","unstructured":"Nannini M, Astolfi A, Urbini M, et al. Integrated genomic study of quadruple-WT GIST (KIT\/PDGFRA\/SDH\/RAS pathway wild-type GIST). BMC Cancer. 2014;14:685.","journal-title":"BMC Cancer"},{"key":"2362_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13569-019-0112-7","volume":"9","author":"MC Heinrich","year":"2019","unstructured":"Heinrich MC, Patterson J, Beadling C, et al. Genomic aberrations in cell cycle genes predict progression of KIT-mutant gastrointestinal stromal tumors (GISTs). Clin Sarcoma Res. 2019;9:3.","journal-title":"Clin Sarcoma Res"},{"key":"2362_CR7","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/ng.3095","volume":"46","author":"W Lee","year":"2014","unstructured":"Lee W, Teckie S, Wiesner T, et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet. 2014;46:1227\u201332.","journal-title":"Nat Genet"},{"key":"2362_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/modpathol.2015.134","volume":"29","author":"IM Schaefer","year":"2016","unstructured":"Schaefer IM, Fletcher CD, Hornick JL. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol. 2016;29:4\u201313.","journal-title":"Mod Pathol"},{"key":"2362_CR9","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1038\/s41436-021-01170-5","volume":"23","author":"E Legius","year":"2021","unstructured":"Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med. 2021;23:1506\u201313.","journal-title":"Genet Med"},{"key":"2362_CR10","first-page":"1057","volume":"54","author":"T Sato","year":"2007","unstructured":"Sato T, Kanda T, Nishikura K, et al. Two cases of gastrointestinal stromal tumor of the stomach with lymph node metastasis. Hepatogastroenterology. 2007;54:1057\u201360.","journal-title":"Hepatogastroenterology"},{"key":"2362_CR11","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1097\/PAS.0000000000000564","volume":"40","author":"CN Prieto-Granada","year":"2016","unstructured":"Prieto-Granada CN, Wiesner T, Messina JL, et al. Loss of H3K27me3 Expression Is a Highly Sensitive Marker for Sporadic and Radiation-induced MPNST. Am J Surg Pathol. 2016;40:479\u201389.","journal-title":"Am J Surg Pathol"},{"key":"2362_CR12","doi-asserted-by":"publisher","first-page":"e2400284","DOI":"10.1200\/PO.24.00284","volume":"8","author":"H Fujii","year":"2024","unstructured":"Fujii H, Hirano H, Shiraishi K, et al. Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database. JCO Precis Oncol. 2024;8:e2400284.","journal-title":"JCO Precis Oncol"},{"key":"2362_CR13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","volume":"149","author":"CV Dang","year":"2012","unstructured":"Dang CV. MYC on the path to cancer. Cell. 2012;149:22\u201335.","journal-title":"Cell"},{"key":"2362_CR14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nature09784","volume":"469","author":"R Margueron","year":"2011","unstructured":"Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011;469:343\u20139.","journal-title":"Nature"},{"key":"2362_CR15","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1101\/gad.1035902","volume":"16","author":"A Kuzmichev","year":"2002","unstructured":"Kuzmichev A, Nishioka K, Erdjument-Bromage H, et al. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 2002;16:2893\u2013905.","journal-title":"Genes Dev"},{"key":"2362_CR16","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1001\/jamaoncol.2016.0264","volume":"2","author":"MA Dickson","year":"2016","unstructured":"Dickson MA, Schwartz GK, Keohan ML, et al. Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. JAMA Oncol. 2016;2:937\u201340.","journal-title":"JAMA Oncol"},{"key":"2362_CR17","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1158\/1535-7163.MCT-24-1027","volume":"24","author":"N Riyahi","year":"2025","unstructured":"Riyahi N, Malko R, Shannon HE, et al. Therapeutic Targeting of BET Proteins in Sarcoma. Mol Cancer Ther. 2025;24:1320\u201330.","journal-title":"Mol Cancer Ther"},{"key":"2362_CR18","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.biopha.2016.04.019","volume":"81","author":"X Song","year":"2016","unstructured":"Song X, Zhang L, Gao T, et al. Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation. Biomed Pharmacother. 2016;81:288\u201394.","journal-title":"Biomed Pharmacother"}],"container-title":["Clinical Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12328-026-02362-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12328-026-02362-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12328-026-02362-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:04:59Z","timestamp":1785463499000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12328-026-02362-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["2362"],"URL":"https:\/\/doi.org\/10.1007\/s12328-026-02362-9","relation":{},"ISSN":["1865-7257","1865-7265"],"issn-type":[{"value":"1865-7257","type":"print"},{"value":"1865-7265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]},"assertion":[{"value":"31 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors declare no conflict of interest for this article.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Consent was obtained from the patient for the publication of this case report.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was not required for this single case report according to the institutional policy. This study was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}}]}}