Genome-wide DNA methylation analysis of pediatric medulloblastomas from a Brazilian cohort: an exploratory study

DNA methylation profiling is a central tool for molecular classification of pediatric medulloblastoma. However, most reference datasets are derived from high-income countries, and the performance of established epigenetic markers in underrepresented populations remains insufficiently explored.

We performed an exploratory genome-wide DNA methylation analysis of 15 pediatric medulloblastomas from a Brazilian cohort using the Illumina Infinium MethylationEPIC v2.0 array. Differentially methylated regions were identified using FDR-corrected statistical analyses and evaluated across molecular subgroups (SHH, Group 3, and Group 4). Functional annotation was conducted to assess biological themes associated with subgroup-enriched methylation patterns.

Methylation profiling revealed largely overlapping epigenetic landscapes among subgroups, alongside a limited number of subgroup-associated differentially methylated regions. These regions were mainly located in regulatory genomic elements and involved genes related to transcriptional regulation and developmental pathways. Several findings were consistent with previously reported subgroup-associated features, while additional loci not commonly included in diagnostic panels were observed.

This exploratory study highlights the importance of validating DNA methylation-based biomarkers across diverse populations. The global methylation patterns observed in this Brazilian cohort were largely consistent with those reported in large international reference datasets, while also underscoring the value of population-aware analyses in expanding the diversity of epigenomic reference data.