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@ARTICLE{Cavalli:136672,
      author       = {F. M. G. Cavalli and J.-M. Hübner$^*$ and T. Sharma$^*$
                      and B. Luu and M. Sill$^*$ and M. Zapotocky and S. C. Mack
                      and H. Witt$^*$ and T. Lin and D. J. H. Shih and B. Ho and
                      M. Santi and L. Emery and J. Hukin and C. Dunham and R. E.
                      McLendon and E. S. Lipp and S. Gururangan and A. Grossbach
                      and P. French and J. M. Kros and M. C. van Veelen and A. A.
                      N. Rao and C. Giannini and S. Leary and S. Jung and C. C.
                      Faria and J. Mora and U. Schüller and M. M. Alonso and J.
                      A. Chan and A. Klekner and L. B. Chambless and E. I. Hwang
                      and M. Massimino and C. G. Eberhart and M. A. Karajannis and
                      B. Lu and L. M. Liau and M. Zollo and V. Ferrucci and C.
                      Carlotti and D. P. C. Tirapelli and U. Tabori and E. Bouffet
                      and M. Ryzhova and D. W. Ellison and T. E. Merchant and M.
                      R. Gilbert and T. S. Armstrong and A. Korshunov$^*$ and S.
                      Pfister$^*$ and M. D. Taylor and K. Aldape and K.
                      Pajtler$^*$ and M. Kool$^*$ and V. Ramaswamy},
      title        = {{H}eterogeneity within the {PF}-{EPN}-{B} ependymoma
                      subgroup.},
      journal      = {Acta neuropathologica},
      volume       = {136},
      number       = {2},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2018-01140},
      pages        = {227 - 237},
      year         = {2018},
      abstract     = {Posterior fossa ependymoma comprise three distinct
                      molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB),
                      and PF-EPN-SE (subependymoma). Clinically, they are very
                      disparate and PFB tumors are currently being considered for
                      a trial of radiation avoidance. However, to move forward,
                      unraveling the heterogeneity within PFB would be highly
                      desirable. To discern the molecular heterogeneity within
                      PFB, we performed an integrated analysis consisting of DNA
                      methylation profiling, copy-number profiling, gene
                      expression profiling, and clinical correlation across a
                      cohort of 212 primary posterior fossa PFB tumors.
                      Unsupervised spectral clustering and t-SNE analysis of
                      genome-wide methylation data revealed five distinct subtypes
                      of PFB tumors, termed PFB1-5, with distinct demographics,
                      copy-number alterations, and gene expression profiles. All
                      PFB subtypes were distinct from PFA and posterior fossa
                      subependymomas. Of the five subtypes, PFB4 and PFB5 are more
                      discrete, consisting of younger and older patients,
                      respectively, with a strong female-gender enrichment in PFB5
                      (age: p = 0.011, gender: p = 0.04). Broad
                      copy-number aberrations were common; however, many events
                      such as chromosome 2 loss, 5 gain, and 17 loss were enriched
                      in specific subtypes and 1q gain was enriched in PFB1. Late
                      relapses were common across all five subtypes, but deaths
                      were uncommon and present in only two subtypes (PFB1 and
                      PFB3). Unlike the case in PFA ependymoma, 1q gain was not a
                      robust marker of poor progression-free survival; however,
                      chromosome 13q loss may represent a novel marker for risk
                      stratification across the spectrum of PFB subtypes. Similar
                      to PFA ependymoma, there exists a significant intertumoral
                      heterogeneity within PFB, with distinct molecular subtypes
                      identified. Even when accounting for this heterogeneity,
                      extent of resection remains the strongest predictor of poor
                      outcome. However, this biological heterogeneity must be
                      accounted for in future preclinical modeling and
                      personalized therapies.},
      cin          = {B062 / G380 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30019219},
      doi          = {10.1007/s00401-018-1888-x},
      url          = {https://inrepo02.dkfz.de/record/136672},
}