Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma
Publication date
2026-02-09
Authors
Bernardi, Flavia
Torrejon, Jacob
Basili, Irene
Van Ommeren, Randy
Marsaud, Véronique
Yu, Hua
Talbot, Julie
Souphron, Judith
Indersie, Emilie
Forget, Antoine
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Supervisors
Document Type
Article
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taverne
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.
Keywords
Taverne, Journal Article
Citation
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, Loew, D, Poullet, P, Liva, S, Lovino, M, Lin, I-H, Nakashima, T, Gharsalli, T, Nicolas, P A, Yubuki, N, Ribas, R A, Colsch, B, Chu-Van, E, Castelli, F, Sampaio, J L, Leboucher, S, Lasgi, C, Besse, L, Soler, M-N, Lo Re, V, Planque, N, Abeysundara, N, Balin, P, Wang, H, Su, H, Wu, X, Cavalli, F M G, Saulnier, O, Ficarra, E, Di Marcotullio, L, Kumegawa, K, Maruyama, R, Kawauchi, D, Picard, D, Remke, M, Riffaud, L, Puiseux, C, Bouchoucha, Y, Huybrechts, S, Simbozel, M, Bourdeaut, F, Varlet, P, Puget, S, Blauwblomme, T, Andrianteranagna, M, Planchon, J M, Dugourd, A, Saez-Rodriguez, J, Barillot, E, Servant, N, Martignetti, L, Rich, J, Kool, M, Pfister, S M, Agnihotri, S, Suzuki, H, Fanjul, M, Wang, W-J, Tsai, J-W, Sun, R C, Beccaria, K, Dufour, C, Sarry, J-E, Michealraj, K A, Taylor, M D & Ayrault, O 2026, 'Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma', Cancer Cell, vol. 44, no. 2, pp. p383-404.e18. https://doi.org/10.1016/j.ccell.2025.12.012