Affiliation:
1. Molecular Oncology Research Center Barretos Cancer Hospital Barretos Brazil
2. Molecular Diagnostic Laboratory Barretos Cancer Hospital Barretos Brazil
3. Department of Pathology Barretos Cancer Hospital Barretos Brazil
4. Ribeirão Preto Medical School University of São Paulo São Paulo Brazil
5. Federal University of São Paulo São Paulo Brazil
6. Italian Hospital of Buenos Aires Buenos Aires Argentina
7. São João Hospital Porto Portugal
8. Pediatric Department Barretos Cancer Hospital Barretos Brazil
9. Life and Health Sciences Research Institute (ICVS), Medical School University of Minho Braga Portugal
Abstract
Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment‐associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin‐Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin‐Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Fundação de Amparo à Pesquisa do Estado de São Paulo
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Hospital de Câncer de Barretos