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000303251 1001_ $$00000-0002-3551-4429$$aApfelbaum, April A$$b0
000303251 245__ $$aA diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas.
000303251 260__ $$a[London]$$bSpringer Nature$$c2025
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000303251 520__ $$aOncogenic alterations in fibroblast growth factor receptor (FGFR)-family proteins occur across cancers, including pediatric gliomas. Our genomic analysis of 11,635 gliomas across ages finds that 5.3% of all gliomas harbor FGFR alterations, with an incidence of almost 9% in pediatric gliomas. Alterations in FGFR proteins are differentially enriched by age, tumor grade, and histology, with FGFR1 alterations associated with glioneuronal histologies. Leveraging isogenic systems, we confirm FGFR1 alterations to induce downstream Mitogen Activated Protein Kinase (MAPK) and mTOR signaling pathways, drive gliomagenesis, activate neuronal transcriptional programs and exhibit sensitivity to MAPK pathway and pan-FGFR inhibitors. Finally, we perform a retrospective analysis of clinical responses in children diagnosed with FGFR-altered gliomas and find that treatment with currently available inhibitors is largely associated with stability of disease. This study provides key insights into the biology of FGFR1-altered gliomas, therapeutic strategies to target them and associated challenges that still need to be overcome.
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000303251 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, Fibroblast Growth Factor, Type 1
000303251 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aFGFR1 protein, human
000303251 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aTOR Serine-Threonine Kinases
000303251 650_7 $$0EC 2.7.1.1$$2NLM Chemicals$$aMTOR protein, human
000303251 650_2 $$2MeSH$$aHumans
000303251 650_2 $$2MeSH$$aGlioma: genetics
000303251 650_2 $$2MeSH$$aGlioma: pathology
000303251 650_2 $$2MeSH$$aGlioma: drug therapy
000303251 650_2 $$2MeSH$$aGlioma: metabolism
000303251 650_2 $$2MeSH$$aChild
000303251 650_2 $$2MeSH$$aReceptor, Fibroblast Growth Factor, Type 1: genetics
000303251 650_2 $$2MeSH$$aReceptor, Fibroblast Growth Factor, Type 1: metabolism
000303251 650_2 $$2MeSH$$aReceptor, Fibroblast Growth Factor, Type 1: antagonists & inhibitors
000303251 650_2 $$2MeSH$$aFemale
000303251 650_2 $$2MeSH$$aBrain Neoplasms: genetics
000303251 650_2 $$2MeSH$$aBrain Neoplasms: pathology
000303251 650_2 $$2MeSH$$aBrain Neoplasms: drug therapy
000303251 650_2 $$2MeSH$$aBrain Neoplasms: metabolism
000303251 650_2 $$2MeSH$$aMale
000303251 650_2 $$2MeSH$$aChild, Preschool
000303251 650_2 $$2MeSH$$aMutation
000303251 650_2 $$2MeSH$$aAdolescent
000303251 650_2 $$2MeSH$$aRetrospective Studies
000303251 650_2 $$2MeSH$$aSignal Transduction
000303251 650_2 $$2MeSH$$aTOR Serine-Threonine Kinases: metabolism
000303251 650_2 $$2MeSH$$aInfant
000303251 650_2 $$2MeSH$$aNeoplasm Grading
000303251 650_2 $$2MeSH$$aCell Line, Tumor
000303251 7001_ $$aMorin, Eric$$b1
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000303251 7001_ $$00009-0002-7972-2892$$aChandarana, Bhavyaa$$b6
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000303251 7001_ $$00000-0001-6267-8595$$aHébert, Steven$$b40
000303251 7001_ $$aPeck, Sydney$$b41
000303251 7001_ $$00000-0001-7807-5393$$aPicca, Alberto$$b42
000303251 7001_ $$00000-0003-4082-7267$$aLarouche, Valérie$$b43
000303251 7001_ $$aRenzi, Samuele$$b44
000303251 7001_ $$00000-0003-4562-1823$$aBuhrlage, Sara J$$b45
000303251 7001_ $$aBale, Tejus A$$b46
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000303251 7001_ $$00000-0002-5910-7799$$aTouat, Mehdi$$b48
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