Molecular profiling of pediatric and adolescent ependymomas: identification of genetic variants using a next-generation sequencing panel

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 ; de Seixas Alves, Maria Teresa ^{[3, 2]} ; Benevides Silva, Frederico Adolfo ^{[4, 2]} ; Dastoli, Patricia Alessandra ^{[5, 2]} ; Cavalheiro, Sergio ^{[5, 2]} ; Caminada de Toledo, Silvia Regina ^{[1, 2, 6]}

Affiliation

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

^[2] Univ Fed Sao Paulo, Pediat Oncol Inst GRA ACC, Dept Pediat, Sao Paulo, SP - Brazil

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

^[4] Univ Fed Sao Paulo, Dept Imaging Diag, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil

^[6] Univ Fed Sao Paulo, Pediat Oncol Inst, Grp Apoio Adolescente Crianca com Canc, 743 Botucatu St 8th Floor Genet Lab, BR-04023062 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEURO-ONCOLOGY; v. 155, n. 1 SEP 2021.
• Web of Science Citations: 0

Abstract

Purpose Ependymoma (EPN) accounts for approximately 10% of all primary central nervous system (CNS) tumors in children and in most cases, chemotherapy is ineffective and treatment remains challenging. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in EPNs of childhood and adolescence, using a next-generation sequencing (NGS) panel specific for pediatric neoplasms. Methods We selected 61 samples with initial diagnosis of EPN from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were divided according to the anatomical compartment of the CNS - 42 posterior fossa (PF), 14 supratentorial (ST), and five spinal (SP). 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 24 of 61 (39.3%) tumors and over 90% of all variants were pathogenic or likely pathogenic. The most commonly variants detected were in CIC, ASXL1, and JAK2 genes and have not been reported in EPN yet. MN1-BEND2 fusion, alteration recently described in a new CNS tumor type, was identified in one ST sample that was reclassified as astroblastoma. Additionally, YAP1-MAMLD1 fusion, a rare event associated with good outcome in ST-EPN, was observed in two patients diagnosed under 2 years old. Conclusions Molecular profiling by the OCCRA (R) panel showed novel alterations in pediatric and adolescent EPNs, which highlights the clinical importance in identifying genetic variants for patients' prognosis and therapeutic orientation. (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