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@ARTICLE{Morfouace:301505,
      author       = {M. Morfouace and F. Bielle and E. Razis and F. Estrade and
                      A. Rubio and F. Bautista and T. de Rojas and M. Vieito and
                      S. Meade and M. Sanson and A. C. Marques and M. Preusser and
                      H. Hatcher and G. P. Balasubramanian$^*$ and E. Pineda and
                      L. D'Hondt and J. Duerinck and A. Michotte and C. Mawrin and
                      T. Ribalta and G. Marucci and V. Golfinopoulos and S. M.
                      Pfister$^*$ and D. T. Jones$^*$ and M. G. McCabe},
      title        = {{M}olecular analysis of adolescent and young adult high
                      grade gliomas in the {SPECTA}-{AYA} study: {P}oorly
                      characterised tumours with frequent germline alterations.},
      journal      = {European journal of cancer},
      volume       = {223},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-01044},
      pages        = {115493},
      year         = {2025},
      abstract     = {Adolescent and young adult (AYA) high grade gliomas (HGG)
                      have the worst survival of AYA malignancies yet are poorly
                      represented in large-scale molecular datasets.50 AYAs aged
                      12-29 with newly diagnosed or recurrent HGG and other high
                      risk central nervous system (CNS) tumours were prospectively
                      recruited to the EORTC SPECTA platform study and underwent
                      whole exome sequencing, RNA sequencing and methylation
                      profiling, with central pathological review. Actionable
                      mutations were reported and patients followed up for
                      therapies and outcome.From 46 locally diagnosed HGGs and 4
                      other recurrent CNS tumours, molecular and pathology review
                      resulted in histological grade re-classification (n = 10),
                      diagnostic refinement (n = 9) and revised diagnoses (n = 12)
                      in a substantial proportion. Pathogenic constitutional
                      alterations were present in 14 $\%$ overall and were largely
                      limited to cases with IDH-wildtype glioblastoma and
                      paediatric-type diffuse HGGs. 91 $\%$ of HGGs had
                      potentially actionable alterations affecting RAS/RAF/MAPK
                      (60 $\%),$ PI3K/AKT/mTOR (27 $\%)$ and cell cycle genes (11
                      $\%).$ High tumour mutational burden (> 10 somatic
                      non-synonymous mutations per Mb of genome targeted) was
                      present in 12 $\%$ at diagnosis and 18 $\%$ at recurrence,
                      all in histological grade 4 tumours. Ten patients' treatment
                      was modified on the basis of molecular profile, of whom 5
                      remained on treatment at last follow-up.AYA HGGs comprise a
                      diverse group of entities; accurate, molecularly-defined
                      diagnosis is critical to direct primary treatment, determine
                      risk of genetic predisposition and guide
                      molecularly-directed therapy. Current services fail to
                      routinely address diagnosis, personalised molecular
                      profiling or investigation of therapeutic opportunities for
                      this high risk, poor prognosis group of rare cancer
                      patients.},
      keywords     = {AYA (Other) / Actionable alterations (Other) / Adolescent
                      (Other) / Constitutional mutations (Other) / High grade
                      glioma (Other) / Young adult (Other)},
      cin          = {B062 / HD01 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40393126},
      doi          = {10.1016/j.ejca.2025.115493},
      url          = {https://inrepo02.dkfz.de/record/301505},
}