Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
18 Apr 2024
18 Apr 2024
Historique:
received:
14
11
2023
accepted:
13
03
2024
medline:
19
4
2024
pubmed:
19
4
2024
entrez:
18
4
2024
Statut:
epublish
Résumé
In vitro models of pediatric brain tumors (pBT) are instrumental for better understanding the mechanisms contributing to oncogenesis and testing new therapies; 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, 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 significantly 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. We identified a set of hypomethylated genes shared among unfaithful cells converging on response to growth factors and migration pathways, such as signaling cascade activation, tissue organization, and cellular migration. In conclusion, DNAm and CNV are informative tools that should be used to assess the recapitulation of pBT-cells from parental tumors.
Identifiants
pubmed: 38637626
doi: 10.1038/s41698-024-00578-x
pii: 10.1038/s41698-024-00578-x
doi:
Types de publication
Journal Article
Langues
eng
Pagination
92Informations de copyright
© 2024. The Author(s).
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