Gliomas in children and adolescents: investigation of molecular alterations with a potential prognostic and therapeutic impact

Author(s)

Cabral de Carvalho Correa, Debora ^{[1, 2]} ; Tesser-Gamba, Francine ^[2] ; Dias Oliveira, Indhira ^[2] ; Saba da Silva, Nasjla ^[2] ; Capellano, Andrea Maria ^[2] ; de Seixas Alves, Maria Teresa ^{[3, 2]} ; Dastoli, Patricia Alessandra ^{[4, 2]} ; Cavalheiro, Sergio ^{[4, 2]} ; Caminada de Toledo, Silvia Regina ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Pediat Oncol Inst, GRA ACC UNIFESP, Dept Pediat, Genet Lab, 743 Botucatu St, 8th Floor Vila Clementi, BR-04023062 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY; v. 148, n. 1 OCT 2021.
• Web of Science Citations: 0

Abstract

Purpose Gliomas represent the most frequent central nervous system (CNS) tumors in children and adolescents. However, therapeutic strategies for these patients, based on tumor molecular profile, are still limited compared to the wide range of treatment options for the adult population. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in gliomas of childhood and adolescence using the next-generation sequencing (NGS) strategy. Methods We selected 95 samples with initial diagnosis of glioma from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were categorized according to the 2021 World Health Organization Classification of Tumors of the CNS, which included 39 low-grade gliomas (LGGs) and 56 high-grade gliomas (HGGs). Four HGG samples were classified as congenital glioblastoma (cGBM). NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay(R) (OCCRA(R)) panel, from Thermo Fisher Scientific(R). Results Genetic variants were identified in 76 of 95 (80%) tumors. In HGGs, the most common molecular alteration detected was H3F3A c.83A > T variant (H3.3 K27M) and co-occurring mutations in ATRX, TP53, PDGFRA, MET, and MYC genes were also frequently observed. One HGG sample was reclassified as supratentorial ependymoma ZFTA-fusion positive after NGS was performed. In LGGs, four KIAA1549-BRAF fusion transcripts were detected and this alteration was the most recurrent genetic event and favorable prognostic factor identified. Additionally, genetic variants in ALK and NTRK genes, which provide potential targets for therapy with Food and Drug Administration-approved drugs, were identified in two different cases of cGBM that were classified as infant-type hemispheric glioma, a newly recognized subgroup of pediatric HGG. Conclusion Molecular profiling by the OCCRA(R) panel comprehensively addressed the most relevant genetic variants in gliomas of childhood and adolescence, as these tumors have specific patterns of molecular alterations, outcomes, and effectiveness to therapies. (AU)

• FAPESP's process: 19/12074-5 - Investigation of genetic alterations of childhood and adolescence ependymomas and gliomas using the new generation sequencing strategy
• Grantee: Débora Cabral de Carvalho Corrêa
• Support Opportunities: Scholarships in Brazil - Master