% 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{Vaillant:310128,
      author       = {J. Vaillant$^*$ and S. Pal and J. Müller$^*$ and A.
                      Wittmann$^*$ and A. Boakye-Yiadom$^*$ and P. Sievers$^*$ and
                      P. Zimmer$^*$ and M. Schoof and F. Schelb$^*$ and N.
                      Hofmann$^*$ and M.-K. Keck$^*$ and T. Fabian$^*$ and U.
                      Schüller and M. Zuckermann$^*$ and R. Beroukhim and P.
                      Bandopadhayay and D. T. W. Jones$^*$ and L. Kutscher$^*$},
      title        = {{A} {C}re-mediated copy number variant compromises the
                      reliability of a {L}ox{P}-{STOP}-{L}ox{P}-{PLAG}1 driven
                      brain tumor model.},
      journal      = {Neuro-oncology advances},
      volume       = {8},
      number       = {1},
      issn         = {2632-2498},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2026-00456},
      pages        = {vdaf251},
      year         = {2026},
      note         = {#EA:B430#LA:B430# / #NCTZFB26# / #DKTKZFB26#},
      abstract     = {The developmental context in which genetic alterations
                      occur is crucial to understand disease progression. In
                      pediatric cancer, modeling tumor formation in the right cell
                      type is necessary to faithfully recapitulate the unique
                      nature of pediatric tumors. The Cre-LoxP system is a
                      powerful tool to modulate gene expression in specific cell
                      types at discrete developmental time windows.We used
                      Cre-LoxP mouse models to study the role of the oncofetal
                      transcription factor PLAG1 in pediatric brain tumor
                      formation. We characterized our model using histology, DNA
                      methylation based copy number variant (CNV) analysis on
                      fresh frozen and FFPE derived samples, RNA sequencing, whole
                      genome sequencing and whole genome CRISPR Cas9 screening.We
                      generated a new model for PLAG1 overexpressing brain tumors,
                      but discovered an unexpected CNV at the Nras locus by DNA
                      methylation analysis. We confirmed the CNV via whole genome
                      sequencing and found that it was likely mediated by
                      Cre-recombination at the transgene insertion site. Both the
                      tumor transcriptome and genetic dependencies are
                      substantially shaped by this CNV.Our work demonstrates the
                      necessity of copy-number analysis when working with
                      transgenic Cre-LoxP mouse models. Assessing CNVs should
                      become a standard evaluation procedure when reporting new
                      tumor models, preventing misleading conclusions that could
                      dramatically impact the reliability of preclinical studies.},
      keywords     = {CNV (Other) / PLAG1 (Other) / animal models (Other) /
                      pediatric brain tumor (Other) / preclinical model (Other)},
      cin          = {B430 / B360 / B062 / B300 / HD02 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B430-20160331 / I:(DE-He78)B360-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)HD02-20160331 / 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:41756758},
      pmc          = {pmc:PMC12932942},
      doi          = {10.1093/noajnl/vdaf251},
      url          = {https://inrepo02.dkfz.de/record/310128},
}