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Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

ABSTRACT: In vitro models of pediatric brain tumors (pBT) are tools instrumental for better understanding the mechanisms contributing to oncogenesis and testing new therapies; and thus, ideally, they should recapitulate the original tumor. We applied DNA methylation (DNAm) and copy number variation (CNV) profiling to characterize 241 pBT samples, including 155 tumors and 86 pBT-derived cell cultures, and considering serum vs serum-free conditions, late vs early passages, and dimensionality (2D vs 3D cultures). We performed a t-SNE classification and identified differentially methylated regions in tumors compared to cell models. Early cell cultures recapitulate the original tumor, but serum media and 2D culturing were demonstrated to significant contribute to the divergence of DNAm profiles from the parental ones. All divergent cells clustered together acquiring a common deregulated epigenetic signature, suggesting a shared selective pressure. In conclusion, DNAm and CNV are informative tools that should be used to assess the recapitulation of pBT-cells from parental tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE225810 | GEO | 2024/03/25

REPOSITORIES: GEO

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