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@ARTICLE{Romanovsky:275438,
      author       = {E. Romanovsky and K. Kluck and I. Ourailidis and M. Menzel
                      and S. Beck and M. Ball and D. Kazdal and P. Christopoulos
                      and P. Schirmacher$^*$ and T. Stiewe and A. Stenzinger$^*$
                      and J. Budczies$^*$},
      title        = {{H}omogenous {TP}53mut-associated tumor biology across
                      mutation and cancer types revealed by transcriptome
                      analysis.},
      journal      = {Cell death discovery},
      volume       = {9},
      number       = {1},
      issn         = {2058-7716},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2023-00761},
      pages        = {126},
      year         = {2023},
      abstract     = {TP53 is the most frequently mutated gene in human cancer.
                      While no TP53-targeting drugs have been approved in the USA
                      or Europe so far, preclinical and clinical studies are
                      underway to investigate targeting of specific or all TP53
                      mutations, for example, by restoration of the functionality
                      of mutated TP53 (TP53mut) or protecting wildtype TP53
                      (TP53wt) from negative regulation. We performed a
                      comprehensive mRNA expression analysis in 24 cancer types of
                      TCGA to extract (i) a consensus expression signature shared
                      across TP53 mutation types and cancer types, (ii)
                      differential gene expression patterns between tumors
                      harboring different TP53 mutation types such as loss of
                      function, gain of function or dominant-negative mutations,
                      and (iii) cancer-type-specific patterns of gene expression
                      and immune infiltration. Analysis of mutational hotspots
                      revealed both similarities across cancer types and cancer
                      type-specific hotspots. Underlying ubiquitous and cancer
                      type-specific mutational processes with the associated
                      mutational signatures contributed to explaining this
                      observation. Virtually no genes were differentially
                      expressed between tumors harboring different TP53 mutation
                      types, while hundreds of genes were over- and underexpressed
                      in TP53mut compared to TP53wt tumors. A consensus list
                      included 178 genes that were overexpressed and 32 genes that
                      were underexpressed in the TP53mut tumors of at least 16 of
                      the investigated 24 cancer types. In an association analysis
                      of immune infiltration with TP53 mutations in 32 cancer
                      subtypes, decreased immune infiltration was observed in six
                      subtypes, increased infiltration in two subtypes, a mixed
                      pattern of decreased and increased immune cell populations
                      in four subtypes, while immune infiltration was not
                      associated with TP53 status in 20 subtypes. The analysis of
                      a large cohort of human tumors complements results from
                      experimental studies and supports the view that TP53
                      mutations should be further evaluated as predictive markers
                      for immunotherapy and targeted therapies.},
      cin          = {HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)HD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37059713},
      doi          = {10.1038/s41420-023-01413-1},
      url          = {https://inrepo02.dkfz.de/record/275438},
}