{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:06:51Z","timestamp":1788887211872,"version":"build-2803163510"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":232,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P20GM130454-06"],"award-info":[{"award-number":["2P20GM130454-06"]}],"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":["P20GM104416"],"award-info":[{"award-number":["P20GM104416"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 10% of glioblastomas harbor targetable genomic fusions. NTRK2 participates in a variety of fusion events that drive tumorigenesis. Two previous reports have described KANK1::NTRK2 fusions in adult glioblastoma patients with poor survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective analysis of glioblastoma patients treated at Dartmouth-Hitchcock Medical Center (DHMC) from 2020 to 2025 to identify cases harboring KANK1::NTRK2 fusions. Clinical presentation, treatment, histopathologic features, and outcomes were reviewed. In addition, we conducted GeoMx whole-transcriptome and high-plex proteomic digital spatial profiling of a KANK1::NTRK2-positive glioblastoma and a comparator tumor from a long-term survivor. Candidate biomarkers were orthogonally validated using immunohistochemistry and\/or immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two patients with KANK1::NTRK2 fusion glioblastoma were identified, both demonstrating rapid progression, therapeutic resistance, and survival of less than 7 months. Proteomic profiling showed increased expression and activation of canonical NTRK2 downstream signaling pathways, particularly MEK1\/2 and ERK1\/2. This was accompanied by upregulation of extracellular matrix remodeling enzymes, including MMP3, MMP14, and ADAM15, along with reduced expression of extracellular matrix-associated transcripts and perineuronal net components in particular compared to a non-fusion glioblastoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These limited, hypothesis-generating findings suggest constitutive NTRK2 signaling may promote coordinated extracellular matrix degradation and remodeling, potentially facilitating rapid and aggressive tumor growth and invasion in a subset of glioblastomas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag219","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:53:00Z","timestamp":1787140380000},"source":"Crossref","is-referenced-by-count":0,"title":["Perineuronal net degradation in aggressive glioblastomas with\n                    <i>KANK1::NTRK2<\/i>\n                    fusions"],"prefix":"10.1093","volume":"8","author":[{"given":"Madhumala K","family":"Sadanandappa","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishika","family":"Karbhari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]},{"name":"Department of Neurology and Medical Oncology, Mayo Clinic , Rochester, Minnesota, USA (N.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brizha","family":"Knowles","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, (B.K.)","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M","family":"Palisoul","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward G","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J","family":"Tafe","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J","family":"Zanazzi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]},{"name":"Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-4287","authenticated-orcid":false,"given":"Chun-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]},{"name":"Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-0495","authenticated-orcid":false,"given":"Jennifer","family":"Hong","sequence":"additional","affiliation":[{"name":"Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire,","place":["USA"]},{"name":"Department of Surgery, Section of Neurosurgery, Dartmouth-Hitchcock 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