The Role of Genetic Profiling in Pediatric Brain Tumors
Year: 2026
Type: article
Abstract: Histopathology and immunohistochemistry alone may be inadequate for accurately classifying diagnostically challenging pediatric central nervous system (CNS) tumors, which comprise a broad and heterogeneous group of more than 100 entities.1 We present nine cases with an unresolved referring diagnosis in which DNA methylation profiling, alone or combined with next-generation sequencing (NGS), established the final diagnosis and describe three illustrative cases in detail to highlight the value of an integrated diagnostic approach.Between 2020 and 2024, 35 children with newly diagnosed CNS tumors were treated at our institution, and 20 underwent molecular profiling at a single reference laboratory: 11 medulloblastomas, profiled to assign the molecular subgroup, and nine tumors with an unresolved referring diagnosis, an indication added later.A referring diagnosis was considered unresolved when a histological diagnosis had been issued but was not securely supported-when the descriptive findings favored a differential diagnosis rather than a single World Health Organization (WHO) 2021 entity, or when the stated entity was not corroborated by immunohistochemistry or by the clinical and radiological findings.Genome-wide DNA methylation was profiled using Illumina Infinium MethylationEPIC (850K) arrays at the Hopp Children's Cancer Center Heidelberg (KiTZ) and the German Cancer Research Center (DKFZ), Germany, and analyzed using the DKFZ brain tumor classifier (versions v11b4, v12.5, or v12.8, according to the year of testing).Calibrated scores of ≥ 0.9 were regarded as high confidence, 0.3-< 0.9 as intermediate confidence, and < 0.3 as no match; copy-number profiles were inferred from the array data, and t-distributed stochastic neighbor embedding (t-SNE) or uniform manifold approximation and projection (UMAP) was used to position each tumor against the reference cohort.Targeted DNA sequencing (panel NPHD2019A or NPHD2022A) and/or RNA sequencing were added in six of the nine cases when the methylation result was
Source: Balkan Medical Journal
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7221884151