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DOI 10.1016/j.ccell.2025.12.012

Медицинская библиотека · Cancer cell · 2026

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

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Аннотация

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.

Для цитирования: 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. Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal group 3 medulloblastoma.. Cancer cell. 2026. DOI: 10.1016/j.ccell.2025.12.012.

Предметные рубрики MeSH

HumansMedulloblastomaMultiomicsLipid MetabolismAnimalsCerebellar NeoplasmsProteomicsProto-Oncogene Proteins c-mycMiceTranscriptomeProteome
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