Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas.
Meningioma
Methylation profile
NF2
Targeted sequencing
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
29
07
2020
accepted:
18
07
2021
revised:
10
07
2021
pubmed:
9
9
2021
medline:
23
2
2022
entrez:
8
9
2021
Statut:
ppublish
Résumé
In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.
Identifiants
pubmed: 34495383
doi: 10.1007/s00401-021-02351-x
pii: 10.1007/s00401-021-02351-x
pmc: PMC8500891
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
873-886Informations de copyright
© 2021. The Author(s).
Références
J Neuropathol Exp Neurol. 2016 Jan;75(1):44-52
pubmed: 26705409
Lancet Oncol. 2011 Dec;12(13):1229-39
pubmed: 22094004
Neuro Oncol. 2017 Aug 1;19(8):1088-1096
pubmed: 28482067
Nat Genet. 2013 Aug;45(8):927-32
pubmed: 23817572
Science. 2013 Mar 1;339(6123):1077-80
pubmed: 23348505
Lancet Oncol. 2017 May;18(5):682-694
pubmed: 28314689
Neuro Oncol. 2017 Mar 1;19(3):345-351
pubmed: 28082415
J Neurosurg. 2004 Feb;100(2 Suppl Pediatrics):179-82
pubmed: 14758946
Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5528-37
pubmed: 27573852
J Neurosurg Pediatr. 2015 Sep;16(3):296-300
pubmed: 26114992
J Natl Cancer Inst. 2015 Dec 13;108(5):
pubmed: 26668184
Neuro Oncol. 2017 Apr 1;19(4):535-545
pubmed: 28170043
Am J Hum Genet. 1994 Jun;54(6):1022-9
pubmed: 7911002
Neurol Med Chir (Tokyo). 2010 Jan;50(1):27-32; discussion 32
pubmed: 20098021
Curr Opin Oncol. 2019 Nov;31(6):562-567
pubmed: 31425178
Br J Neurosurg. 2016 Oct;30(5):571-6
pubmed: 27173440
Acta Neuropathol Commun. 2020 Apr 3;8(1):41
pubmed: 32245394
Acta Neuropathol. 2020 Jan;139(1):215-218
pubmed: 31734728
Nat Genet. 2013 Mar;45(3):285-9
pubmed: 23334667
Genes Chromosomes Cancer. 1994 Jun;10(2):122-30
pubmed: 7520265
Nat Commun. 2017 Aug 4;8(1):186
pubmed: 28775249
Brain Pathol. 2003 Jul;13(3):386-408
pubmed: 12946028
Cancer Cell. 2012 Oct 16;22(4):425-37
pubmed: 23079654
Nature. 2018 Mar 22;555(7697):469-474
pubmed: 29539639
Nat Rev Neurol. 2018 Feb;14(2):106-115
pubmed: 29302064
Acta Neuropathol. 2017 Jul;134(1):155-158
pubmed: 28474103
Histopathology. 2017 Apr;70(5):814-820
pubmed: 27891692
J Neuropathol Exp Neurol. 2001 Oct;60(10):994-1003
pubmed: 11589430
Neuro Oncol. 2018 Nov 12;20(12):1584-1593
pubmed: 30010853
Neuro Oncol. 2015 Jan;16 Suppl 10:x1-x36
pubmed: 25542864
Clin Cancer Res. 2013 Mar 1;19(5):1180-9
pubmed: 23406776
Childs Nerv Syst. 2015 Mar;31(3):441-7
pubmed: 25249420
JAMA Neurol. 2017 Sep 1;74(9):1123-1129
pubmed: 28759666
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Acta Neuropathol. 2013 Mar;125(3):351-8
pubmed: 23404370
Brain Pathol. 2020 Nov;30(6):1134-1143
pubmed: 32716568
Neuropathology. 2018 Feb;38(1):22-33
pubmed: 28901666
Nat Genet. 1994 Feb;6(2):180-4
pubmed: 8162072
Am J Surg Pathol. 1998 Dec;22(12):1482-90
pubmed: 9850174
Neuro Oncol. 2017 Oct 19;19(11):1447-1456
pubmed: 28482042
Acta Neuropathol. 2016 Jun;131(6):903-10
pubmed: 26671409
Neuro Oncol. 2016 Jan;18 Suppl 1:i1-i50
pubmed: 26705298