Home > Publications database > A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas. > print

001     303251
005     20250803021929.0
024 7 _ |a 10.1038/s41467-025-61820-z
|2 doi
024 7 _ |a pmid:40744913
|2 pmid
024 7 _ |a altmetric:179842501
|2 altmetric
037 _ _ |a DKFZ-2025-01596
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Apfelbaum, April A
|0 0000-0002-3551-4429
|b 0
245 _ _ |a A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1754055359_19093
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a 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.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
|0 G:(DE-HGF)POF4-312
|c POF4-312
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a Receptor, Fibroblast Growth Factor, Type 1
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a FGFR1 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a TOR Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a MTOR protein, human
|0 EC 2.7.1.1
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Glioma: genetics
|2 MeSH
650 _ 2 |a Glioma: pathology
|2 MeSH
650 _ 2 |a Glioma: drug therapy
|2 MeSH
650 _ 2 |a Glioma: metabolism
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Receptor, Fibroblast Growth Factor, Type 1: genetics
|2 MeSH
650 _ 2 |a Receptor, Fibroblast Growth Factor, Type 1: metabolism
|2 MeSH
650 _ 2 |a Receptor, Fibroblast Growth Factor, Type 1: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Brain Neoplasms: genetics
|2 MeSH
650 _ 2 |a Brain Neoplasms: pathology
|2 MeSH
650 _ 2 |a Brain Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Brain Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a Adolescent
|2 MeSH
650 _ 2 |a Retrospective Studies
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a TOR Serine-Threonine Kinases: metabolism
|2 MeSH
650 _ 2 |a Infant
|2 MeSH
650 _ 2 |a Neoplasm Grading
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
700 1 _ |a Morin, Eric
|b 1
700 1 _ |a Sturm, Dominik
|0 P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807
|b 2
|u dkfz
700 1 _ |a Ayoub, Georges
|0 0000-0002-1694-6779
|b 3
700 1 _ |a DiGiacomo, Jeromy
|b 4
700 1 _ |a Bahadur, Sher
|b 5
700 1 _ |a Chandarana, Bhavyaa
|0 0009-0002-7972-2892
|b 6
700 1 _ |a Power, Phoebe C
|b 7
700 1 _ |a Cusick, Margaret M
|b 8
700 1 _ |a Novikov, Dana
|0 0000-0002-1388-9270
|b 9
700 1 _ |a Prabhakar, Prem
|b 10
700 1 _ |a Jones, Robert E
|b 11
700 1 _ |a Vogelzang, Jayne
|b 12
700 1 _ |a Bossi, Connor C
|b 13
700 1 _ |a Malinowski, Seth
|b 14
700 1 _ |a Woodward, Lewis M
|b 15
700 1 _ |a Jones, Tania A
|0 0000-0002-0067-3382
|b 16
700 1 _ |a Jeang, John
|b 17
700 1 _ |a Lamson, Sarah W
|b 18
700 1 _ |a Collins, Jared
|0 0009-0006-7184-3875
|b 19
700 1 _ |a Cai, Kelly Y
|0 0009-0001-2556-4844
|b 20
700 1 _ |a Jones, Jacquelyn S
|b 21
700 1 _ |a Oh, Sehee
|b 22
700 1 _ |a Jeon, Hyesung
|0 0000-0002-0034-5469
|b 23
700 1 _ |a Wang, Jinhua
|0 0000-0002-1214-4103
|b 24
700 1 _ |a Cameron, Amy
|b 25
700 1 _ |a Rechter, Patrick
|0 0009-0009-5160-2996
|b 26
700 1 _ |a De Leon, Angela
|b 27
700 1 _ |a Murugesan, Karthikeyan
|0 0000-0002-2275-1126
|b 28
700 1 _ |a Montesion, Meagan
|0 0000-0001-9155-556X
|b 29
700 1 _ |a Albacker, Lee A
|0 0000-0002-5070-1783
|b 30
700 1 _ |a Ramkissoon, Shakti H
|b 31
700 1 _ |a van Tilburg, Cornelis Martinus
|0 P:(DE-He78)a6b5fcabf661bef95109dbee87dc5271
|b 32
|u dkfz
700 1 _ |a Hardin, Emily C
|0 P:(DE-He78)953707d4b9faf5d9183b719847bd99f0
|b 33
|u dkfz
700 1 _ |a Sievers, Philipp
|0 P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6
|b 34
|u dkfz
700 1 _ |a Sahm, Felix
|0 P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88
|b 35
|u dkfz
700 1 _ |a Yeo, Kee Kiat
|0 0000-0003-0713-6384
|b 36
700 1 _ |a Rosenberg, Tom
|0 0000-0002-9592-2539
|b 37
700 1 _ |a Chi, Susan N
|0 0000-0001-7753-878X
|b 38
700 1 _ |a Wright, Karen D
|b 39
700 1 _ |a Hébert, Steven
|0 0000-0001-6267-8595
|b 40
700 1 _ |a Peck, Sydney
|b 41
700 1 _ |a Picca, Alberto
|0 0000-0001-7807-5393
|b 42
700 1 _ |a Larouche, Valérie
|0 0000-0003-4082-7267
|b 43
700 1 _ |a Renzi, Samuele
|b 44
700 1 _ |a Buhrlage, Sara J
|0 0000-0003-4562-1823
|b 45
700 1 _ |a Bale, Tejus A
|b 46
700 1 _ |a Smith, Amy A
|b 47
700 1 _ |a Touat, Mehdi
|0 0000-0002-5910-7799
|b 48
700 1 _ |a Jabado, Nada
|0 0000-0003-2485-3692
|b 49
700 1 _ |a Fischer, Eric S
|0 0000-0001-7337-6306
|b 50
700 1 _ |a Eck, Michael J
|b 51
700 1 _ |a Baird, Lissa
|b 52
700 1 _ |a Witt, Olaf
|0 P:(DE-He78)143af26de9d57bf624771616318aaf7c
|b 53
|u dkfz
700 1 _ |a Kleinman, Claudia L
|0 0000-0002-5158-7126
|b 54
700 1 _ |a Nguyen, Quang-De
|b 55
700 1 _ |a Sheer, Denise
|0 0000-0001-9067-1796
|b 56
700 1 _ |a Alexandrescu, Sanda
|b 57
700 1 _ |a Jones, David
|0 P:(DE-He78)551bb92841f634070997aa168d818492
|b 58
|u dkfz
700 1 _ |a Ligon, Keith L
|0 0000-0002-7733-600X
|b 59
700 1 _ |a Bandopadhayay, Pratiti
|0 0000-0002-4175-4760
|b 60
773 _ _ |a 10.1038/s41467-025-61820-z
|g Vol. 16, no. 1, p. 7018
|0 PERI:(DE-600)2553671-0
|n 1
|p 7018
|t Nature Communications
|v 16
|y 2025
|x 2041-1723
909 C O |o oai:inrepo02.dkfz.de:303251
|p VDB
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 2
|6 P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 32
|6 P:(DE-He78)a6b5fcabf661bef95109dbee87dc5271
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 33
|6 P:(DE-He78)953707d4b9faf5d9183b719847bd99f0
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 34
|6 P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 35
|6 P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 53
|6 P:(DE-He78)143af26de9d57bf624771616318aaf7c
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 58
|6 P:(DE-He78)551bb92841f634070997aa168d818492
913 1 _ |a DE-HGF
|b Gesundheit
|l Krebsforschung
|1 G:(DE-HGF)POF4-310
|0 G:(DE-HGF)POF4-312
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Funktionelle und strukturelle Genomforschung
|x 0
914 1 _ |y 2025
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2024-01-30T07:48:07Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Peer review
|d 2024-01-30T07:48:07Z
915 _ _ |a Creative Commons Attribution CC BY (No Version)
|0 LIC:(DE-HGF)CCBYNV
|2 V:(DE-HGF)
|b DOAJ
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1060
|2 StatID
|b Current Contents - Agriculture, Biology and Environmental Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-01-02
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-01-02
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2025-01-02
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2025-01-02
920 1 _ |0 I:(DE-He78)B360-20160331
|k B360
|l Pädiatrische Gliomforschung
|x 0
920 1 _ |0 I:(DE-He78)B300-20160331
|k B300
|l KKE Neuropathologie
|x 1
920 1 _ |0 I:(DE-He78)HD01-20160331
|k HD01
|l DKTK HD zentral
|x 2
920 1 _ |0 I:(DE-He78)B310-20160331
|k B310
|l KKE Pädiatrische Onkologie
|x 3
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-He78)B360-20160331
980 _ _ |a I:(DE-He78)B300-20160331
980 _ _ |a I:(DE-He78)HD01-20160331
980 _ _ |a I:(DE-He78)B310-20160331
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21