ArticleNature communications2025
A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
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6citing papers in PubMed
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Who cites it
6 citing papers in PubMed.
- Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma.Neuro-oncology · 2026Review
- Advances in the management of pediatric low-grade glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- PTPN11-related Noonan syndrome predisposes to multifocal low-grade CNS tumors harboring FGFR1 variants.Journal of neuro-oncology · 2026Article
- PTPN11-Related Noonan Syndrome Predisposes to Multifocal Low-Grade CNS Tumors Harboring FGFR1 Variants.Research square · 2026Article
- Report from the National Pediatric Cancer Foundation - infantile glioma and other non-embryonal central nervous system tumors: evolving molecular advances and current treatment landscape.Frontiers in oncology · 2026Review
- Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors.The EMBO journal · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
61 authors.
April A Apfelbaum *Department of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3551-4429
Eric Morin *Department of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Dominik SturmDivision of Pediatric Glioma Research, Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0250-1696
Georges AyoubDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1694-6779
Jeromy DiGiacomoDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Sher BahadurDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Bhavyaa ChandaranaLady Davis Research Institute, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0009-0002-7972-2892
Phoebe C PowerDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Margaret M CusickDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Dana NovikovDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1388-9270
Prem PrabhakarDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Robert E JonesDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jayne VogelzangDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Connor C BossiDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Seth MalinowskiDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Lewis M WoodwardBlizard Institute, Queen Mary University of London, London, UK.
Tania A JonesBlizard Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-0067-3382
John JeangDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Sarah W LamsonDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Jared CollinsDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0009-0006-7184-3875
Kelly Y CaiDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0009-0001-2556-4844
Jacquelyn S JonesDepartment of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sehee OhDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hyesung JeonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0034-5469
Jinhua WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1214-4103
Amy CameronLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Patrick RechterLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0009-0009-5160-2996
Angela De LeonDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Karthikeyan MurugesanComputational Discovery, Foundation Medicine Inc, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2275-1126
Meagan MontesionComputational Discovery, Foundation Medicine Inc, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9155-556X
Lee A AlbackerComputational Discovery, Foundation Medicine Inc, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5070-1783
Shakti H RamkissoonPathology, Foundation Medicine Inc, Boston, MA, USA.
Cornelis M van TilburgNational Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5274-910X
Emily C HardinNational Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Philipp SieversHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-3237-6021
Felix SahmGerman Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5441-1962
Kee Kiat YeoDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0713-6384
Tom RosenbergDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9592-2539
Susan N ChiDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7753-878X
Karen D WrightDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Steven HébertLady Davis Research Institute, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-6267-8595
Sydney PeckOrlando Health- Arnold Palmer Hospital for Children, Orlando, FL, USA.
Alberto PiccaSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau - Paris Brain Institute (ICM), AP-HP, Pitié Salpêtrière University Hospital, Paris, France.ORCID http://orcid.org/0000-0001-7807-5393
Valérie LaroucheDepartment of Pediatrics, Hemato-Oncology, CHU de Québec-Université Laval, Quebec City, QC, Canada.ORCID http://orcid.org/0000-0003-4082-7267
Samuele RenziDivision of Pediatric Hematology-Oncology, Chul-Québec, Quebec City, QC, Canada.
Sara J BuhrlageDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4562-1823
Tejus A BaleDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Amy A SmithOrlando Health- Arnold Palmer Hospital for Children, Orlando, FL, USA.
Mehdi TouatSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau - Paris Brain Institute (ICM), AP-HP, Pitié Salpêtrière University Hospital, Paris, France.ORCID http://orcid.org/0000-0002-5910-7799
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0003-2485-3692
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7337-6306
Michael J EckDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Lissa BairdDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Olaf WittNational Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-3918-9157
Claudia L KleinmanLady Davis Research Institute, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-5158-7126
Quang-De NguyenLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Denise SheerBlizard Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0001-9067-1796
Sanda AlexandrescuDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
David T W JonesDivision of Pediatric Glioma Research, Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2036-5141
Keith L LigonBroad Institute of MIT and Harvard, Cambridge, MA, USA. keith_ligon@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-7733-600X
Pratiti BandopadhayayDepartment of Pediatric Oncology, Dana-Farber Cancer/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA. Pratiti_Bandopadhayay@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-4175-4760
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MDamon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) 03-24NCI NIH HHS P30 CA008748
Abstract
Oncogenic 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.
Indexed as
Brain NeoplasmsGliomaMutationReceptor, Fibroblast Growth Factor, Type 1AdolescentCell Line, TumorChildChild, PreschoolFemaleHumansInfantMaleNeoplasm GradingRetrospective StudiesSignal TransductionTOR Serine-Threonine KinasesFGFR1 protein, humanMTOR protein, humanReceptor, Fibroblast Growth Factor, Type 1TOR Serine-Threonine Kinases
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