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@ARTICLE{Jahn:166582,
      author       = {N. Jahn and T. Terzer$^*$ and E. Sträng and A. Dolnik and
                      S. Cocciardi and E. Panina and A. Corbacioglu and J. Herzig
                      and D. Weber and A. Schrade and K. Götze and T. Schröder
                      and M. Lübbert and D. Wellnitz and E. Koller and R. F.
                      Schlenk and V. I. Gaidzik and P. Paschka and F. G. Rücker
                      and M. Heuser and F. Thol and A. Ganser and A. Benner$^*$
                      and H. Döhner and L. Bullinger and K. Döhner},
      title        = {{G}enomic heterogeneity in core-binding factor acute
                      myeloid leukemia and its clinical implication.},
      journal      = {Blood advances},
      volume       = {4},
      number       = {24},
      issn         = {2473-9537},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2020-03025},
      pages        = {6342 - 6352},
      year         = {2020},
      abstract     = {Core-binding factor (CBF) acute myeloid leukemia (AML)
                      encompasses AML with inv(16)(p13.1q22) and AML with
                      t(8;21)(q22;q22.1). Despite sharing a common pathogenic
                      mechanism involving rearrangements of the CBF
                      transcriptional complex, there is growing evidence for
                      considerable genotypic heterogeneity. We comprehensively
                      characterized the mutational landscape of 350 adult CBF-AML
                      [inv(16): n = 160, t(8;21): n = 190] performing targeted
                      sequencing of 230 myeloid cancer-associated genes. Apart
                      from common mutations in signaling genes, mainly NRAS, KIT,
                      and FLT3, both CBF-AML entities demonstrated a remarkably
                      diverse pattern with respect to the underlying cooperating
                      molecular events, in particular in genes encoding for
                      epigenetic modifiers and the cohesin complex. In addition,
                      recurrent mutations in novel collaborating candidate genes
                      such as SRCAP $(5\%$ overall) and DNM2 $(6\%$ of t(8;21)
                      AML) were identified. Moreover, aberrations altering
                      transcription and differentiation occurred at earlier
                      leukemic stages and preceded mutations impairing
                      proliferation. Lasso-penalized models revealed an inferior
                      prognosis for t(8;21) AML, trisomy 8, as well as FLT3 and
                      KIT exon 17 mutations, whereas NRAS and WT1 mutations
                      conferred superior prognosis. Interestingly, clonal
                      heterogeneity was associated with a favorable prognosis.
                      When entering mutations by functional groups in the model,
                      mutations in genes of the methylation group (ie, DNMT3A,
                      TET2) had a strong negative prognostic impact.},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33351131},
      doi          = {10.1182/bloodadvances.2020002673},
      url          = {https://inrepo02.dkfz.de/record/166582},
}