{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:42:21Z","timestamp":1790034141427,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 CA217694"],"award-info":[{"award-number":["P50 CA217694"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017050","name":"Cycle for Survival","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024990","name":"National Yang Ming Chiao Tung University","doi-asserted-by":"publisher","award":["112\u2010V\u2010A\u2010002"],"award-info":[{"award-number":["112\u2010V\u2010A\u2010002"]}],"id":[{"id":"10.13039\/501100024990","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Risk stratification across the three main clinical subsets of malignant peripheral nerve sheath tumor (MPNST), neurofibromatosis type I (NF1\u2010related), sporadic, and prior radiation therapy (RT), is based mainly on clinicopathologic parameters, such as size, grade, stage, and NF1 status. Moreover, no prior study investigated the additional impact of genomic alterations in the prognosis of high\u2010grade MPNST using clinically validated DNA targeted next\u2010generation sequencing (NGS) panels. Our goal was to integrate clinicopathologic and genomic parameters using an elastic\u2010net penalized Cox proportional hazards machine learning model using OncoCast for risk prediction. Herein we perform comprehensive mutational and copy number profiling using Memorial Sloan Kettering\u2013Integrated Mutation Profiling of Actionable Cancer Targets (MSK\u2010IMPACT) on 81 primary localized high\u2010grade MPNSTs (51% NF1\u2010related, 38% sporadic, 11% RT\u2010associated). The most common genomic alterations included\n                    <jats:italic>NF1<\/jats:italic>\n                    (51% germline, 59% somatic),\n                    <jats:italic>CDKN2A\/B<\/jats:italic>\n                    (62%), PRC2 components (\n                    <jats:italic>SUZ12<\/jats:italic>\n                    ,\n                    <jats:italic>EED<\/jats:italic>\n                    ) (53%), and\n                    <jats:italic>TP53<\/jats:italic>\n                    (25%). Variables selected by OncoCast as significantly associated with survival were used to construct a three\u2010tier risk stratification model for progression\u2010free survival (PFS) and disease\u2010specific survival (DSS). For PFS, patients with chr16 deletion were classified as high\u2010risk, those with concurrent germline and somatic\n                    <jats:italic>NF1<\/jats:italic>\n                    alterations as low\u2010risk, and the remainder was assigned to the intermediate\u2010risk group. For DSS, cases with fraction genome altered (FGA)\u2009&gt;\u200950% were defined as high\u2010risk, those with\n                    <jats:italic>PRC2<\/jats:italic>\n                    abnormalities,\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    deletion,\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter mutation, or chr16 deletion as intermediate\u2010risk, and cases lacking all the aforementioned alterations as low\u2010risk. The high\u2010risk group showed significantly inferior survival compared to the low\u2010risk group (both PFS and DSS\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Subgroup analysis showed that among NF1\u2010related MPNST, co\u2010occurring somatic\n                    <jats:italic>NF1<\/jats:italic>\n                    mutation or WT\n                    <jats:italic>TP53<\/jats:italic>\n                    was associated with superior PFS. Collectively, genomic alterations detected by clinical NGS panels provide potential new biomarkers for risk stratification that can be integrated with conventional parameters to provide improved prognostication and guide therapeutic strategies. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70051","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:16:02Z","timestamp":1774066562000},"page":"248-259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel genomic risk stratification model for primary high\u2010grade malignant peripheral nerve sheath tumor (\n                    <scp>MPNST<\/scp>\n                    )"],"prefix":"10.1002","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8121-8322","authenticated-orcid":false,"given":"Hsin\u2010Yi","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K","family":"Dermawan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tap","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Surgery Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"},{"name":"Human Oncology Pathogenesis Program Memorial Sloan Kettering Cancer Center  New York NY USA"},{"name":"Weill Cornell Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-8205","authenticated-orcid":false,"given":"Cristina R","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.03.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.05.010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae235"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3095"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157502"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-020-02036-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03181-4"},{"key":"e_1_2_9_9_1","article-title":"Survival after resection of malignant peripheral nerve sheath tumors: introducing and validating a novel type\u2010specific prognostic model","volume":"6","author":"Acem I","year":"2024","journal-title":"Neurooncol 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