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@ARTICLE{Maas:176974,
      author       = {S. L. N. Maas$^*$ and D. Stichel$^*$ and T. Hielscher$^*$
                      and P. Sievers$^*$ and A. S. Berghoff and D. Schrimpf$^*$
                      and M. Sill$^*$ and P. Euskirchen and C. Blume$^*$ and A.
                      Patel Jamilkhan$^*$ and H. Dogan$^*$ and D. Reuss$^*$ and H.
                      Dohmen and M. Stein and A. Reinhardt$^*$ and A. K.
                      Suwala$^*$ and A. Wefers$^*$ and P. Baumgarten and F.
                      Ricklefs and E. J. Rushing and M. Bewerunge-Hudler$^*$ and
                      R. Ketter and J. Schittenhelm and Z. Jaunmuktane and S. Leu
                      and F. E. A. Greenway and L. R. Bridges and T. Jones and C.
                      Grady and J. Serrano and J. Golfinos and C. Sen and C.
                      Mawrin and C. Jungk and D. Hänggi and M. Westphal and K.
                      Lamszus and N. Etminan and G. Jungwirth and C. Herold-Mende
                      and A. Unterberg and P. Harter$^*$ and H.-G. Wirsching and
                      M. C. Neidert and M. Ratliff and M. Platten and M. Snuderl
                      and K. D. Aldape and S. Brandner and J. Hench and S. Frank
                      and S. M. Pfister$^*$ and D. Jones$^*$ and G.
                      Reifenberger$^*$ and T. Acker and W. Wick$^*$ and M. Weller
                      and M. Preusser and A. von Deimling$^*$ and F. Sahm$^*$},
      collaboration = {G. C. o. A. Meningiomas},
      title        = {{I}ntegrated {M}olecular-{M}orphologic {M}eningioma
                      {C}lassification: {A} {M}ulticenter {R}etrospective
                      {A}nalysis, {R}etrospectively and {P}rospectively
                      {V}alidated.},
      journal      = {Journal of clinical oncology},
      volume       = {39},
      number       = {34},
      issn         = {1527-7755},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2021-02207},
      pages        = {3839-3852},
      year         = {2021},
      note         = {#EA:B300#LA:B300# / 2021 Dec 1;39(34):3839-3852},
      abstract     = {Meningiomas are the most frequent primary intracranial
                      tumors. Patient outcome varies widely from benign to highly
                      aggressive, ultimately fatal courses. Reliable
                      identification of risk of progression for individual
                      patients is of pivotal importance. However, only biomarkers
                      for highly aggressive tumors are established (CDKN2A/B and
                      TERT), whereas no molecularly based stratification exists
                      for the broad spectrum of patients with low- and
                      intermediate-risk meningioma.DNA methylation data and
                      copy-number information were generated for 3,031 meningiomas
                      (2,868 patients), and mutation data for 858 samples. DNA
                      methylation subgroups, copy-number variations (CNVs),
                      mutations, and WHO grading were analyzed. Prediction power
                      for outcome was assessed in a retrospective cohort of 514
                      patients, validated on a retrospective cohort of 184, and on
                      a prospective cohort of 287 multicenter cases.Both CNV- and
                      methylation family-based subgrouping independently resulted
                      in increased prediction accuracy of risk of recurrence
                      compared with the WHO classification (c-indexes WHO 2016,
                      CNV, and methylation family 0.699, 0.706, and 0.721,
                      respectively). Merging all risk stratification approaches
                      into an integrated molecular-morphologic score resulted in
                      further substantial increase in accuracy (c-index 0.744).
                      This integrated score consistently provided superior
                      accuracy in all three cohorts, significantly outperforming
                      WHO grading (c-index difference P = .005). Besides the
                      overall stratification advantage, the integrated score
                      separates more precisely for risk of progression at the
                      diagnostically challenging interface of WHO grade 1 and
                      grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34
                      [1.28-8.72] retrospective and prospective validation
                      cohorts, respectively).Merging these layers of histologic
                      and molecular data into an integrated, three-tiered score
                      significantly improves the precision in meningioma
                      stratification. Implementation into diagnostic routine
                      informs clinical decision making for patients with
                      meningioma on the basis of robust outcome prediction.},
      cin          = {B300 / HD01 / C060 / B062 / W110 / FM01 / B360 / ED01 /
                      B320},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)W110-20160331 / I:(DE-He78)FM01-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)ED01-20160331 /
                      I:(DE-He78)B320-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34618539},
      doi          = {10.1200/JCO.21.00784},
      url          = {https://inrepo02.dkfz.de/record/176974},
}