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@ARTICLE{Wang:303088,
      author       = {P. Wang and R. Sen and F. Buchholz$^*$ and S. Sayed},
      title        = {{A} base editing platform for the correction of cancer
                      driver mutations unmasks conserved p53 transcription
                      programs.},
      journal      = {Genome biology},
      volume       = {26},
      number       = {1},
      issn         = {1465-6906},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-01513},
      pages        = {217},
      year         = {2025},
      abstract     = {Understanding the role of cancer hotspot mutations is
                      essential for unraveling mechanisms of tumorigenesis and
                      identifying therapeutic vulnerabilities. Correcting cancer
                      mutations with base editing is a novel, yet promising
                      approach for investigating the biology of driver
                      mutations.Here, we present a versatile platform to
                      investigate the functional impact of cancer hotspot
                      mutations through adenine base editing in combination with
                      transcriptomic profiling. Using this approach, we correct
                      TP53 hotspot mutations in cancer cell lines derived from
                      diverse tissues, followed by mRNA sequencing to evaluate
                      transcriptional changes. Remarkably, correcting these
                      mutations not only reveals the dependency on mutant allele
                      expression but also restores highly conserved
                      tumor-suppressive transcriptional programs, irrespective of
                      tissue origin or co-occurring mutations, highlighting a
                      shared p53-dependent regulatory network. Our findings
                      demonstrate the utility of this base editing platform to
                      systematically interrogate the functional consequences of
                      cancer-associated mutations and their downstream effects on
                      gene expression.This work establishes a robust framework for
                      studying the transcriptional dynamics of cancer hotspot
                      mutations and sheds light on the conserved biological
                      processes reinstated by p53 correction, offering potential
                      avenues for future targeted therapies.},
      keywords     = {Humans / Tumor Suppressor Protein p53: genetics / Tumor
                      Suppressor Protein p53: metabolism / Mutation / Neoplasms:
                      genetics / Gene Editing: methods / Cell Line, Tumor /
                      Transcription, Genetic / Gene Expression Regulation,
                      Neoplastic / Base editing (Other) / CRISPR (Other) / Cancer
                      (Other) / Driver mutation (Other) / P53 (Other) / SMAD4
                      (Other) / Transcriptomics (Other) / Tumor Suppressor Protein
                      p53 (NLM Chemicals) / TP53 protein, human (NLM Chemicals)},
      cin          = {DD01},
      ddc          = {570},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40696461},
      doi          = {10.1186/s13059-025-03667-7},
      url          = {https://inrepo02.dkfz.de/record/303088},
}