Medulloblastoma, the most common malignant brain tumor of childhood, exhibits significant biological complexity that demands deeper exploration. Here, we present a large multiomics dataset integrating data from 384 primary medulloblastoma patient samples across five omic layers: CpG methylome, transcriptome, proteome, phosphoproteome, and metabolome, paired with associated clinical metadata. Data integration revealed intertumoral heterogeneity of lipid metabolism across proteomic subtypes. Notably, while the MYC-FASN-SCD axis drives lipid biosynthesis, pathway inhibition elicits a compensatory escape mechanism in vivo through exogenous fatty acid uptake. Unexpectedly, we demonstrated that MYC triggers lipid storage, creating a unique dependency on lipid droplet-mitochondria communications to sustain tumor maintenance in vivo. Together, this comprehensive analysis reveals a targetable vulnerability downstream of MYC that constitutes a promising therapeutic approach to treat currently untreatable medulloblastoma subtypes.
Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma / Bernardi, F., Torrejon, J., Basili, I., Van Ommeren, R., Marsaud, V., Yu, H., Talbot, J., Souphron, J., Indersie, E., Forget, A., Bonneau, B., Massiot, A., Alcazar, C., Figeac, L., Bonerandi, E., Cancila, G., Sirbu, O., Yadav, N., Mohanakrishnan, D., Lombard, B., et al.. - In: CANCER CELL. - ISSN 1535-6108. - 44:2(2026), pp. 383-404. [10.1016/j.ccell.2025.12.012]
Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma
Basili, IreneCo-primo
;Di Marcotullio, Lucia;
2026
Abstract
Medulloblastoma, the most common malignant brain tumor of childhood, exhibits significant biological complexity that demands deeper exploration. Here, we present a large multiomics dataset integrating data from 384 primary medulloblastoma patient samples across five omic layers: CpG methylome, transcriptome, proteome, phosphoproteome, and metabolome, paired with associated clinical metadata. Data integration revealed intertumoral heterogeneity of lipid metabolism across proteomic subtypes. Notably, while the MYC-FASN-SCD axis drives lipid biosynthesis, pathway inhibition elicits a compensatory escape mechanism in vivo through exogenous fatty acid uptake. Unexpectedly, we demonstrated that MYC triggers lipid storage, creating a unique dependency on lipid droplet-mitochondria communications to sustain tumor maintenance in vivo. Together, this comprehensive analysis reveals a targetable vulnerability downstream of MYC that constitutes a promising therapeutic approach to treat currently untreatable medulloblastoma subtypes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
