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@ARTICLE{Coltin:170386,
      author       = {H. Coltin and L. Sundaresan and K. S. Smith and P. Skowron
                      and L. Massimi and C. G. Eberhart and K. C. Schreck and N.
                      Gupta and W. A. Weiss and D. Tirapelli and C. Carlotti and
                      K. K. W. Li and M. Ryzhova and A. Golanov and O. Zheludkova
                      and O. Absalyamova and K. Okonechnikov$^*$ and D.
                      Stichel$^*$ and A. von Deimling$^*$ and C. Giannini and S.
                      Raskin and E. G. Van Meir and J. A. Chan and D. Fults and L.
                      B. Chambless and S.-K. Kim and A. Vasiljevic and C.
                      Faure-Conter and R. Vibhakar and S. Jung and S. Leary and J.
                      Mora and R. E. McLendon and I. F. Pollack and P. Hauser and
                      W. A. Grajkowska and J. B. Rubin and M. C. van Veelen and P.
                      J. French and J. M. Kros and L. M. Liau and S. M.
                      Pfister$^*$ and M. Kool$^*$ and N. Kijima and M. D. Taylor
                      and R. J. Packer and P. A. Northcott and A. Korshunov$^*$
                      and V. Ramaswamy},
      title        = {{S}ubgroup and subtype-specific outcomes in adult
                      medulloblastoma.},
      journal      = {Acta neuropathologica},
      volume       = {142},
      number       = {5},
      issn         = {1432-0533},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2021-01895},
      pages        = {859-871},
      year         = {2021},
      note         = {#LA:B300# / 2021 Nov;142(5):859-871},
      abstract     = {Medulloblastoma, a common pediatric malignant central
                      nervous system tumour, represent a small proportion of brain
                      tumours in adults. Previously it has been shown that in
                      adults, Sonic Hedgehog (SHH)-activated tumours predominate,
                      with Wingless-type (WNT) and Group 4 being less common, but
                      molecular risk stratification remains a challenge. We
                      performed an integrated analysis consisting of genome-wide
                      methylation profiling, copy number profiling, somatic
                      nucleotide variants and correlation of clinical variables
                      across a cohort of 191 adult medulloblastoma cases
                      identified through the Medulloblastoma Advanced Genomics
                      International Consortium. We identified 30 WNT, 112 SHH, 6
                      Group 3, and 41 Group 4 tumours. Patients with SHH tumours
                      were significantly older at diagnosis compared to other
                      subgroups (p < 0.0001). Five-year progression-free survival
                      (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4
                      (48.0-86.5), $61.9\%$ (51.6-74.2), $80.0\%$ $(95\%$ CI
                      51.6-100.0), and $44.9\%$ $(95\%$ CI 28.6-70.7),
                      respectively (p = 0.06). None of the clinical variables
                      (age, sex, metastatic status, extent of resection,
                      chemotherapy, radiotherapy) were associated with
                      subgroup-specific PFS. Survival among patients with SHH
                      tumours was significantly worse for cases with chromosome 3p
                      loss (HR 2.9, $95\%$ CI 1.1-7.6; p = 0.02), chromosome 10q
                      loss (HR 4.6, $95\%$ CI 2.3-9.4; p < 0.0001), chromosome 17p
                      loss (HR 2.3, $95\%$ CI 1.1-4.8; p = 0.02), and PTCH1
                      mutations (HR 2.6, $95\%$ CI 1.1-6.2; p = 0.04). The
                      prognostic significance of 3p loss and 10q loss persisted in
                      multivariable regression models. For Group 4 tumours,
                      chromosome 8 loss was strongly associated with improved
                      survival, which was validated in a non-overlapping cohort
                      (combined cohort HR 0.2, $95\%$ CI 0.1-0.7; p = 0.007).
                      Unlike in pediatric medulloblastoma, whole chromosome 11
                      loss in Group 4 and chromosome 14q loss in SHH was not
                      associated with improved survival, where MYCN, GLI2 and MYC
                      amplification were rare. In sum, we report unique
                      subgroup-specific cytogenetic features of adult
                      medulloblastoma, which are distinct from those in younger
                      patients, and correlate with survival disparities. Our
                      findings suggest that clinical trials that incorporate new
                      strategies tailored to high-risk adult medulloblastoma
                      patients are urgently needed.},
      keywords     = {Adult (Other) / DNA methylation profiling (Other) /
                      Medulloblastoma (Other) / Molecular groups (Other) / Risk
                      stratification (Other)},
      cin          = {B062 / B300},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34409497},
      doi          = {10.1007/s00401-021-02358-4},
      url          = {https://inrepo02.dkfz.de/record/170386},
}