Highlights
- •The study of archival pediatric HGG samples provided valuable insights, including novel genetic features and subtypes, in this rare tumor type.
- •The use of gold standard karyotyping combined with array and sequencing in a lab without methylation array allowed for reclassification of all tumors.
- •The use of the 2021 WHO classification of CNS tumors refined each integrated tumor diagnosis.
Abstract
Though rare, pediatric high-grade gliomas (pHGG) are a leading cause of cancer-related
mortality in children. We wanted to determine whether our currently available clinical
laboratory methods could better define diagnosis for pHGG that had been archived at
our institution for the past 20 years (1998 to 2017). We investigated 33 formalin-fixed
paraffin-embedded pHGG using ThermoFisher Oncoscan SNP microarray with somatic mutation
analysis, Sanger sequencing, and whole genome sequencing. These data were correlated
with historical histopathological, chromosomal, clinical, and radiological data. Tumors
were subsequently classified according to the 2021 WHO Classification of Paediatric
CNS Tumours. All 33 tumors were found to have genetic aberrations that placed them
within a 2021 WHO subtype and/or provided prognostic information; 6 tumors were upgraded
from WHO CNS grade 3 to grade 4. New pHGG genetic features were found including two
small cell glioblastomas with H3 G34 mutations not previously described; one tumor
with STRN-NTRK2 fusion; and a congenital diffuse leptomeningeal glioneuronal tumor without a chromosomal
1p deletion but with KIAA1549-BRAF fusion. Overall, the combination of laboratory methods yielded key information for
tumor classification. Thus, even small studies of these uncommon tumor types may yield
new genetic features and possible new subtypes that warrant future investigations.
Keywords
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Article info
Publication history
Published online: March 03, 2023
Accepted:
February 28,
2023
Received in revised form:
February 23,
2023
Received:
December 16,
2022
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
