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Gliomas in children and adolescents: investigation of molecular alterations with a potential prognostic and therapeutic impact
- Source :
- Journal of cancer research and clinical oncology. 148(1)
- Publication Year :
- 2021
-
Abstract
- 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. 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® (OCCRA®) panel, from Thermo Fisher Scientific®. 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. Molecular profiling by the OCCRA® 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.
- Subjects :
- Oncology
Ependymoma
Male
Proto-Oncogene Proteins B-raf
Cancer Research
medicine.medical_specialty
Adolescent
DNA Copy Number Variations
Childhood cancer
PDGFRA
World health
Histones
Internal medicine
Glioma
medicine
Biomarkers, Tumor
Humans
Genetic Predisposition to Disease
Child
Gene
ATRX
Retrospective Studies
Hematology
business.industry
Brain Neoplasms
Infant, Newborn
Genetic Variation
High-Throughput Nucleotide Sequencing
Infant
Membrane Proteins
General Medicine
medicine.disease
Child, Preschool
Female
business
Subjects
Details
- ISSN :
- 14321335
- Volume :
- 148
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of cancer research and clinical oncology
- Accession number :
- edsair.doi.dedup.....4739575d4481865419d13ace91248935