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Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)

Fisher, Michael J. ; Jones, David T.W. ; Li, Yimei ; Guo, Xiaofan ; Sonawane, Poonam S. ; Waanders, Angela J. ; Phillips, Joanna J. ; Weiss, William A. ; Resnick, Adam C. and Gosline, Sara , et al. (2021) In Acta Neuropathologica 141(4). p.605-617
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FGFR1, Methylation, Neurofibromatosis, Pediatric brain tumor, Pilocytic astrocytoma
in
Acta Neuropathologica
volume
141
issue
4
pages
605 - 617
publisher
Springer
external identifiers
  • pmid:33585982
  • scopus:85101052488
ISSN
0001-6322
DOI
10.1007/s00401-021-02276-5
language
English
LU publication?
yes
id
6e2eb44b-02cc-4a93-9698-022f66f8b961
date added to LUP
2021-03-05 09:05:36
date last changed
2024-11-15 01:10:54
@article{6e2eb44b-02cc-4a93-9698-022f66f8b961,
  abstract     = {{<p>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.</p>}},
  author       = {{Fisher, Michael J. and Jones, David T.W. and Li, Yimei and Guo, Xiaofan and Sonawane, Poonam S. and Waanders, Angela J. and Phillips, Joanna J. and Weiss, William A. and Resnick, Adam C. and Gosline, Sara and Banerjee, Jineta and Guinney, Justin and Gnekow, Astrid and Kandels, Daniela and Foreman, Nicholas K. and Korshunov, Andrey and Ryzhova, Marina and Massimi, Luca and Gururangan, Sri and Kieran, Mark W. and Wang, Zhihong and Fouladi, Maryam and Sato, Mariko and Øra, Ingrid and Holm, Stefan and Markham, Stephen J. and Beck, Pengbo and Jäger, Natalie and Wittmann, Andrea and Sommerkamp, Alexander C. and Sahm, Felix and Pfister, Stefan M. and Gutmann, David H.}},
  issn         = {{0001-6322}},
  keywords     = {{FGFR1; Methylation; Neurofibromatosis; Pediatric brain tumor; Pilocytic astrocytoma}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  pages        = {{605--617}},
  publisher    = {{Springer}},
  series       = {{Acta Neuropathologica}},
  title        = {{Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)}},
  url          = {{http://dx.doi.org/10.1007/s00401-021-02276-5}},
  doi          = {{10.1007/s00401-021-02276-5}},
  volume       = {{141}},
  year         = {{2021}},
}