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, Flavia; Torrejon, Jacob; Basili, Irene; Van Ommeren, Randy; Marsaud, Véronique; Yu, Hua; Talbot, Julie; Souphron, Judith; Indersie, Emilie; Forget, Antoine; Bonneau, Benjamin; Massiot, Alexane; Alcazar, Coralie; Figeac, Laurine; Bonerandi, Emma; Cancila, Gabriele; Sirbu, Olga; Yadav, Navneesh; Mohanakrishnan, Dinesh; Lombard, Bérangère; Loew, Damarys; Poullet, Patrick; Liva, Stephane; Lovino, Marta; Lin, I-Hsuan; Nakashima, Takuma; Gharsalli, Tarek; Nicolas, Paul Antoine; Yubuki, Naoji; Ribas, Roberto A.; Colsch, Benoit; Chu-Van, Emeline; Castelli, Florence; Sampaio, Julio Lopes; Leboucher, Sophie; Lasgi, Charlene; Besse, Laetitia; Soler, Marie-Noëlle; Lo Re, Valentina; Planque, Nathalie; Abeysundara, Namal; Balin, Polina; Wang, Hao; Su, Haipeng; Wu, Xiaochong; Cavalli, Florence M. G.; Saulnier, Olivier; Ficarra, Elisa; Di Marcotullio, Lucia; Kumegawa, Kohei; Maruyama, Reo; Kawauchi, Daisuke; Picard, Daniel; Remke, Marc; Riffaud, Laurent; Puiseux, Chloé; Bouchoucha, Yassine; Huybrechts, Sophie; Simbozel, Marie; Bourdeaut, Franck; Varlet, Pascale; Puget, Stéphanie; Blauwblomme, Thomas; Andrianteranagna, Mamy; Planchon, Julien Masliah; Dugourd, Aurelien; Saez-Rodriguez, Julio; Barillot, Emmanuel; Servant, Nicolas; Martignetti, Loredana; Rich, Jeremy; Kool, Marcel; Pfister, Stefan M.; Agnihotri, Sameer; Suzuki, Hiromichi; Fanjul, Marjorie; Wang, Won-Jing; Tsai, Jin-Wu; Sun, Ramon C.; Beccaria, Kévin; Dufour, Christelle; Sarry, Jean-Emmanuel; Michealraj, Kulandaimanuvel Antony; Taylor, Michael D.; Ayrault, Olivier. - 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.
