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@ARTICLE{Funke:276420,
      author       = {V. L. E. Funke and C. Walter and V. Melcher and L. Wei and
                      S. Sandmann and M. Hotfilder and J. Varghese and N.
                      Jäger$^*$ and M. Kool$^*$ and D. T. W. Jones$^*$ and S. M.
                      Pfister$^*$ and T. Milde$^*$ and M. Mynarek and S. Rutkowski
                      and J. Seggewiss and D. Jeising and F. W. de Faria and T.
                      Marquardt and T. K. Albert and U. Schüller and K. Kerl},
      title        = {{G}roup-specific cellular metabolism in {M}edulloblastoma.},
      journal      = {Journal of translational medicine},
      volume       = {21},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-01103},
      pages        = {363},
      year         = {2023},
      abstract     = {Cancer metabolism influences multiple aspects of
                      tumorigenesis and causes diversity across malignancies.
                      Although comprehensive research has extended our knowledge
                      of molecular subgroups in medulloblastoma (MB), discrete
                      analysis of metabolic heterogeneity is currently lacking.
                      This study seeks to improve our understanding of metabolic
                      phenotypes in MB and their impact on patients' outcomes.Data
                      from four independent MB cohorts encompassing 1,288 patients
                      were analysed. We explored metabolic characteristics of 902
                      patients (ICGC and MAGIC cohorts) on bulk RNA level.
                      Moreover, data from 491 patients (ICGC cohort) were searched
                      for DNA alterations in genes regulating cell metabolism. To
                      determine the role of intratumoral metabolic differences, we
                      examined single-cell RNA-sequencing (scRNA-seq) data from 34
                      additional patients. Findings on metabolic heterogeneity
                      were correlated to clinical data.Established MB groups
                      exhibit substantial differences in metabolic gene
                      expression. By employing unsupervised analyses, we
                      identified three clusters of group 3 and 4 samples with
                      distinct metabolic features in ICGC and MAGIC cohorts.
                      Analysis of scRNA-seq data confirmed our results of
                      intertumoral heterogeneity underlying the according
                      differences in metabolic gene expression. On DNA level, we
                      discovered clear associations between altered regulatory
                      genes involved in MB development and lipid metabolism.
                      Additionally, we determined the prognostic value of
                      metabolic gene expression in MB and showed that expression
                      of genes involved in metabolism of inositol phosphates and
                      nucleotides correlates with patient survival.Our research
                      underlines the biological and clinical relevance of
                      metabolic alterations in MB. Thus, distinct metabolic
                      signatures presented here might be the first step towards
                      future metabolism-targeted therapeutic options.},
      keywords     = {Inositol phosphates (Other) / Medulloblastoma (Other) /
                      Metabolism (Other) / Nucleotides (Other) / RNA-Seq (Other)},
      cin          = {B062 / HD01 / B360 / B310},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)B310-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37277823},
      doi          = {10.1186/s12967-023-04211-6},
      url          = {https://inrepo02.dkfz.de/record/276420},
}