Integrated genetic profiling of archival pediatric high-grade glial tumors and reassessment with 2021 WHO classification of paediatric CNS tumours

• Published in: Cancer genetics Vol. 274-275; pp. 10 - 20
• Main Authors: Cooley, Linda D, Lansdon, Lisa A, Laurence, Kris, Herriges, John C, Zhang, Lei, Repnikova, Elena A, Joyce, Julie, Thakor, Preeti, Warren, Lisa, Smith, Scott C, Yoo, Byunggil, Gener, Melissa, Ginn, Kevin F, Farooqi, Midhat S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2023
• Subjects: Brain Neoplasms - genetics; Brain Neoplasms - pathology; Central Nervous System Neoplasms - genetics; Child; Glioma - genetics; Glioma - pathology; High-grade glioma; Humans; Karyotype; Mutation - genetics; OncoScan microarray; Pediatric; Sequencing; World Health Organization; OncoScan microarray; High-grade glioma; Pediatric; Sequencing; Karyotype
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2023.02.004

•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. 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determine whether our currently available clinical laboratory methods could better define diagnosis for pHGG that had been archived at our institution for the past 20 years (1998 to 2017).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.