{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T23:38:01Z","timestamp":1782517081466,"version":"3.54.5"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Cancer Center Support"},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P30 CA046934"],"award-info":[{"award-number":["P30 CA046934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012869","name":"Morgan Adams Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012869","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Luke Morin Foundation"},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P01 CA096832"],"award-info":[{"award-number":["P01 CA096832"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Diffuse midline gliomas (DMGs) are incurable pediatric tumors with extraordinarily limited treatment options. Decades of clinical trials combining conventional chemotherapies with radiation therapy have failed to improve these outcomes, demonstrating the need to identify and validate druggable biologic targets within this disease. NTRK1\/2\/3 fusions are found in a broad range of pediatric cancers, including high-grade gliomas and a subset of DMGs. Phase 1\/2 studies of TRK inhibitors have demonstrated good tolerability, effective CNS penetration, and promising objective responses across all patients with TRK fusion-positive cancers, but their use has not been explored in TRK fusion-positive DMG. Here, we report 3 cases of NTRK fusions co-occurring within H3K27M-positive pontine diffuse midline gliomas. We employ a combination of single-cell and bulk transcriptome sequencing from TRK fusion-positive DMG to describe the phenotypic consequences of this co-occurring alteration. We then use ex vivo short-culture assays to evaluate the potential response to TRK inhibition in this disease. Together, these data highlight the importance of routine molecular characterization of these highly aggressive tumors and identify a small subset of patients that may benefit from currently available targeted therapies.<\/jats:p>","DOI":"10.1093\/jnen\/nlab016","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T09:37:58Z","timestamp":1616405878000},"page":"345-353","source":"Crossref","is-referenced-by-count":8,"title":["NTRK Fusions Can Co-Occur With H3K27M Mutations and May Define Druggable Subclones Within Diffuse Midline Gliomas"],"prefix":"10.1093","volume":"80","author":[{"given":"Nathan A","family":"Dahl","sequence":"first","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"},{"name":"Center for Cancer and Blood Disorders, Children\u2019s Hospital Colorado , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M","family":"Donson","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Sanford","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faye M","family":"Walker","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Gilani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"},{"name":"Department of Pathology, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K","family":"Foreman","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"},{"name":"Center for Cancer and Blood Disorders, Children\u2019s Hospital Colorado , Aurora, Colorado, USA"},{"name":"Department of Neurosurgery, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Tinkle","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne J","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey M","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Center for Cancer and Blood Disorders, Phoenix Children\u2019s Hospital , Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Vibhakar","sequence":"additional","affiliation":[{"name":"From the Morgan Adams Foundation Pediatric Brain Tumor Research Program , Aurora, Colorado, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado, USA"},{"name":"Center for Cancer and Blood Disorders, Children\u2019s Hospital Colorado , Aurora, Colorado, USA"},{"name":"Department of Neurosurgery, University of Colorado School of Medicine , Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"2024032523391774000_nlab016-B1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ctrv.2011.06.007","article-title":"Diffuse intrinsic pontine gliomas: A systematic update on clinical trials and biology","volume":"38","author":"Jansen","year":"2012","journal-title":"Cancer Treat Rev"},{"key":"2024032523391774000_nlab016-B2","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1200\/JCO.2017.75.9308","article-title":"Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): A collaborative report from the International and European Society for Pediatric Oncology DIPG Registries","volume":"36","author":"Hoffman","year":"2018","journal-title":"J Clin Oncol"},{"key":"2024032523391774000_nlab016-B3","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/neuonc\/noy070","article-title":"Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma","volume":"20","author":"Gupta","year":"2018","journal-title":"Neuro Oncol"},{"key":"2024032523391774000_nlab016-B4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11060-011-0704-4","article-title":"Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: Advancing basic and translational research and cooperation in DIPG","volume":"105","author":"Bartels","year":"2011","journal-title":"J Neurooncol"},{"key":"2024032523391774000_nlab016-B5","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of tumors of the central nervous system: A 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screening","volume":"37","author":"Albert","year":"2019","journal-title":"J Clin Oncol"},{"key":"2024032523391774000_nlab016-B9","doi-asserted-by":"crossref","first-page":"e000023","DOI":"10.1136\/esmoopen-2015-000023","article-title":"NTRK gene fusions as novel targets of cancer therapy across multiple tumour types","volume":"1","author":"Amatu","year":"2016","journal-title":"ESMO Open"},{"key":"2024032523391774000_nlab016-B10","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/dneu.20769","article-title":"On the death TRK","volume":"70","author":"Harel","year":"2010","journal-title":"Dev Neurobiol"},{"key":"2024032523391774000_nlab016-B11","first-page":"1","article-title":"Growth, survival and migration: The TRK to cancer","volume":"115","author":"Rubin","year":"2003","journal-title":"Cancer Treat Res"},{"key":"2024032523391774000_nlab016-B12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0304-3835(01)00530-4","article-title":"TRK receptor tyrosine 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A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues","volume":"115","author":"Sheng","year":"2001","journal-title":"Am J Clin Pathol"},{"key":"2024032523391774000_nlab016-B14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pathol.2015.11.007","article-title":"Congenital mesoblastic nephroma: A study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement","volume":"48","author":"El Demellawy","year":"2016","journal-title":"Pathology"},{"key":"2024032523391774000_nlab016-B15","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1158\/1078-0432.CCR-08-0651","article-title":"On TRK \u2013 The TRKB signal transduction pathway is an increasingly important target in cancer biology","volume":"15","author":"Thiele","year":"2009","journal-title":"Clin Cancer 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