% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Fernandez:307431,
      author       = {N. R. Fernandez and Y. Chang and N. M. Nunes and J. R.
                      Dimayacyac and A. Levine and A. Ringel and L. Negm and A. B.
                      Ercan and J. M. Hess and O. Ahmad$^*$ and C. Lee and L.
                      Stengs and V. Bianchi and M. Edwards and S. Doherty and J.
                      Chung and L. Nobre and J. Bennett and A. J. Dodgshun and D.
                      Jones$^*$ and S. Pfister$^*$ and A. Villani and D. Malkin
                      and V. Ramaswamy and A. Huang and E. Bouffet and M. Aronson
                      and P. B. Dirks and A. Shlien and G. Getz and Y. E. Maruvka
                      and B. Ertl-Wagner and C. Hawkins and A. Das and U. Tabori},
      title        = {{P}atterns of hypermutation shape tumorigenesis and
                      immunotherapy response in mismatch-repair-deficient glioma.},
      journal      = {Nature genetics},
      volume       = {nn},
      issn         = {1061-4036},
      address      = {London},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2025-03030},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Primary mismatch-repair-deficient high-grade gliomas
                      (priMMRD-HGG) are lethal tumors characterized by
                      hypermutation, resistance to chemoradiation and variable
                      response to immunotherapy. To investigate the mechanisms
                      governing the emergence of driver mutations and their impact
                      on gliomagenesis and patient outcomes, we analyzed genomic
                      and clinical data from 162 priMMRD-HGG. Here we identified
                      three subgroups defined by secondary driver mutations in
                      replicative DNA polymerases or IDH1. These subgroups
                      converge on glioma drivers through distinct combinations of
                      genomic instability-generating mechanisms, displaying an
                      inverse correlation between point mutations and copy number
                      alterations. MMRD signatures drive the emergence of specific
                      mutations in TP53 and IDH1, notably excluding common
                      pediatric glioma drivers. Global hypomethylation stratifies
                      priMMRD-HGG into a unique methylation cluster.
                      DNA-polymerasemut priMMRD-HGG exhibit ultrahypermutation, an
                      immune-hot microenvironment and immunotherapy
                      responsiveness, whereas IDH1mut priMMRD-HGG are immune-cold
                      and immunotherapy resistant. MMRD-driven gliomagenesis
                      defines the role of nonrandom mutagenesis patterns in cancer
                      development, providing frameworks for targeted and
                      immune-therapeutics.},
      cin          = {B360 / B062 / HD01},
      ddc          = {570},
      cid          = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41430480},
      doi          = {10.1038/s41588-025-02420-x},
      url          = {https://inrepo02.dkfz.de/record/307431},
}