Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas
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Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas. / Kirches, Elmar; Sahm, Felix; Korshunov, Andrey; Bluecher, Christina; Waldt, Natalie; Kropf, Siegfried; Schrimpf, Daniel; Sievers, Philipp; Stichel, Damian; Schüller, Ulrich; Schittenhelm, Jens; Riemenschneider, Markus J; Karajannis, Matthias A; Perry, Arie; Pietsch, Torsten; Boekhoff, Svenja; Capper, David; Beck, Katja; Paramasivam, Nagarajan; Schlesner, Matthias; Brastianos, Priscilla K; Müller, Hermann L; Pfister, Stefan M; Mawrin, Christian.
In: ACTA NEUROPATHOL, Vol. 142, No. 5, 11.2021, p. 873-886.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas
AU - Kirches, Elmar
AU - Sahm, Felix
AU - Korshunov, Andrey
AU - Bluecher, Christina
AU - Waldt, Natalie
AU - Kropf, Siegfried
AU - Schrimpf, Daniel
AU - Sievers, Philipp
AU - Stichel, Damian
AU - Schüller, Ulrich
AU - Schittenhelm, Jens
AU - Riemenschneider, Markus J
AU - Karajannis, Matthias A
AU - Perry, Arie
AU - Pietsch, Torsten
AU - Boekhoff, Svenja
AU - Capper, David
AU - Beck, Katja
AU - Paramasivam, Nagarajan
AU - Schlesner, Matthias
AU - Brastianos, Priscilla K
AU - Müller, Hermann L
AU - Pfister, Stefan M
AU - Mawrin, Christian
N1 - © 2021. The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Child
KW - Child, Preschool
KW - Female
KW - Gene Expression Profiling
KW - Humans
KW - Male
KW - Meningeal Neoplasms/genetics
KW - Meningioma/genetics
KW - Transcriptome
U2 - 10.1007/s00401-021-02351-x
DO - 10.1007/s00401-021-02351-x
M3 - SCORING: Journal article
C2 - 34495383
VL - 142
SP - 873
EP - 886
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 5
ER -