Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1).
FGFR1
Methylation
Neurofibromatosis
Pediatric brain tumor
Pilocytic astrocytoma
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
18
12
2020
accepted:
22
01
2021
revised:
21
01
2021
pubmed:
16
2
2021
medline:
16
11
2021
entrez:
15
2
2021
Statut:
ppublish
Résumé
Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.
Identifiants
pubmed: 33585982
doi: 10.1007/s00401-021-02276-5
pii: 10.1007/s00401-021-02276-5
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
605-617Références
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