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Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma

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, trans...

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Main Authors: Bernardi, Flavia (Author) , Torrejon, Jacob (Author) , Basili, Irene (Author) , Van Ommeren, Randy (Author) , Marsaud, Véronique (Author) , Yu, Hua (Author) , Talbot, Julie (Author) , Souphron, Judith (Author) , Indersie, Emilie (Author) , Forget, Antoine (Author) , Bonneau, Benjamin (Author) , Massiot, Alexane (Author) , Alcazar, Coralie (Author) , Figeac, Laurine (Author) , Bonerandi, Emma (Author) , Cancila, Gabriele (Author) , Sirbu, Olga (Author) , Yadav, Navneesh (Author) , Mohanakrishnan, Dinesh (Author) , Lombard, Bérangère (Author) , Loew, Damarys (Author) , Poullet, Patrick (Author) , Liva, Stephane (Author) , Lovino, Marta (Author) , Lin, I-Hsuan (Author) , Nakashima, Takuma (Author) , Gharsalli, Tarek (Author) , Nicolas, Paul Antoine (Author) , Yubuki, Naoji (Author) , Ribas, Roberto A. (Author) , Colsch, Benoit (Author) , Chu-Van, Emeline (Author) , Castelli, Florence (Author) , Sampaio, Julio Lopes (Author) , Leboucher, Sophie (Author) , Lasgi, Charlene (Author) , Besse, Laetitia (Author) , Soler, Marie-Noëlle (Author) , Lo Re, Valentina (Author) , Planque, Nathalie (Author) , Abeysundara, Namal (Author) , Balin, Polina (Author) , Wang, Hao (Author) , Su, Haipeng (Author) , Wu, Xiaochong (Author) , Cavalli, Florence M. G. (Author) , Saulnier, Olivier (Author) , Ficarra, Elisa (Author) , Di Marcotullio, Lucia (Author) , Kumegawa, Kohei (Author) , Maruyama, Reo (Author) , Kawauchi, Daisuke (Author) , Picard, Daniel (Author) , Remke, Marc (Author) , Riffaud, Laurent (Author) , Puiseux, Chloé (Author) , Bouchoucha, Yassine (Author) , Huybrechts, Sophie (Author) , Simbozel, Marie (Author) , Bourdeaut, Franck (Author) , Varlet, Pascale (Author) , Puget, Stéphanie (Author) , Blauwblomme, Thomas (Author) , Andrianteranagna, Mamy (Author) , Planchon, Julien Masliah (Author) , Dugourd, Aurélien (Author) , Sáez Rodríguez, Julio (Author) , Barillot, Emmanuel (Author) , Servant, Nicolas (Author) , Martignetti, Loredana (Author) , Rich, Jeremy (Author) , Kool, Marcel (Author) , Pfister, Stefan (Author) , Agnihotri, Sameer (Author) , Suzuki, Hiromichi (Author) , Fanjul, Marjorie (Author) , Wang, Won-Jing (Author) , Tsai, Jin-Wu (Author) , Sun, Ramon C. (Author) , Beccaria, Kévin (Author) , Dufour, Christelle (Author) , Sarry, Jean-Emmanuel (Author) , Michealraj, Kulandaimanuvel Antony (Author) , Taylor, Michael D. (Author) , Ayrault, Olivier (Author)
Format: Article (Journal)
Language:English
Published: February 9, 2026
In: Cancer cell
Year: 2026, Volume: 44, Issue: 2, Pages: 383-404.e18
ISSN:1878-3686
DOI:10.1016/j.ccell.2025.12.012
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ccell.2025.12.012
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S153561082500546X
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Author Notes:Flavia Bernardi, Jacob Torrejon, Irene Basili, Randy Van Ommeren, Véronique Marsaud, Hua Yu, Julie Talbot, Judith Souphron, Emilie Indersie, Antoine Forget, Benjamin Bonneau, Alexane Massiot, Coralie Alcazar, Laurine Figeac, Emma Bonerandi, Gabriele Cancila, Olga Sirbu, Navneesh Yadav, Dinesh Mohanakrishnan, Bérangère Lombard, Damarys Loew, Patrick Poullet, Stephane Liva, Marta Lovino, I-Hsuan Lin, Takuma Nakashima, Tarek Gharsalli, Paul Antoine Nicolas, Naoji Yubuki, Roberto A. Ribas, Benoit Colsch, Emeline Chu-Van, Florence Castelli, Julio Lopes Sampaio, Sophie Leboucher, Charlene Lasgi, Laetitia Besse, Marie-Noëlle Soler, Valentina Lo Re, Nathalie Planque, Namal Abeysundara, Polina Balin, Hao Wang, Haipeng Su, Xiaochong Wu, Florence M. G. Cavalli, Olivier Saulnier, Elisa Ficarra, Lucia Di Marcotullio, Kohei Kumegawa, Reo Maruyama, Daisuke Kawauchi, Daniel Picard, Marc Remke, Laurent Riffaud, Chloé Puiseux, Yassine Bouchoucha, Sophie Huybrechts, Marie Simbozel, Franck Bourdeaut, Pascale Varlet, Stéphanie Puget, Thomas Blauwblomme, Mamy Andrianteranagna, Julien Masliah Planchon, Aurelien Dugourd, Julio Saez-Rodriguez, Emmanuel Barillot, Nicolas Servant, Loredana Martignetti, Jeremy Rich, Marcel Kool, Stefan M. Pfister, Sameer Agnihotri, Hiromichi Suzuki, Marjorie Fanjul, Won-Jing Wang, Jin-Wu Tsai, Ramon C. Sun, Kévin Beccaria, Christelle Dufour, Jean-Emmanuel Sarry, Kulandaimanuvel Antony Michealraj, Michael D. Taylor, Olivier Ayrault
Description
Summary: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.
Item Description:Gesehen am 06.07.2026
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2025.12.012

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