Journal Article

DKFZ-2026-00133

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. ; 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.DKFZ* ; Pfister, S. M.DKFZ* ; 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
Cell Press Cambridge, Mass.

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.

Keyword(s): lipid biosynthesis ; lipid droplets ; lipid oxidative stress ; medulloblastoma ; metabolomics ; multiomics integration ; pediatric cancer ; phosphoproteomics ; proteomics ; transcriptomics

Note: #DKTKZFB26# / #NCTZFB26# / epub

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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