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@ARTICLE{Wang:282521,
      author       = {X. Wang and A. P. Kutschat and J. Aggrey-Fynn and F. H.
                      Hamdan and R. P. Graham and A. Q. Wixom and Y. Souto and S.
                      Ladigan-Badura and J. A. Yonkus and A. M. Abdelrahman and R.
                      Alva-Ruiz and J. Gaedcke and P. Ströbel and R. L. Kosinsky
                      and F. Wegwitz and P. Hermann and M. J. Truty and J.
                      Siveke$^*$ and S. A. Hahn and E. Hessmann and S. A. Johnsen
                      and Z. Najafova},
      title        = {{I}dentification of a Δ{N}p63-{D}ependent {B}asal-{L}ike
                      {A} {S}ubtype-{S}pecific {T}ranscribed {E}nhancer {P}rogram
                      ({B}-{STEP}) in {A}ggressive {P}ancreatic {D}uctal
                      {A}denocarcinoma.},
      journal      = {Molecular cancer research},
      volume       = {21},
      number       = {9},
      issn         = {1541-7786},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2023-01810},
      pages        = {881 - 891},
      year         = {2023},
      abstract     = {A major hurdle to the application of precision oncology in
                      pancreatic cancer is the lack of molecular stratification
                      approaches and targeted therapy for defined molecular
                      subtypes. In this work, we sought to gain further insight
                      and identify molecular and epigenetic signatures of the
                      Basal-like A pancreatic ductal adenocarcinoma (PDAC)
                      subgroup that can be applied to clinical samples for patient
                      stratification and/or therapy monitoring. We generated and
                      integrated global gene expression and epigenome mapping data
                      from patient-derived xenograft models to identify
                      subtype-specific enhancer regions that were validated in
                      patient-derived samples. In addition, complementary nascent
                      transcription and chromatin topology (HiChIP) analyses
                      revealed a Basal-like A subtype-specific transcribed
                      enhancer program in PDAC characterized by enhancer RNA
                      (eRNA) production that is associated with more frequent
                      chromatin interactions and subtype-specific gene activation.
                      Importantly, we successfully confirmed the validity of eRNA
                      detection as a possible histologic approach for PDAC patient
                      stratification by performing RNA-ISH analyses for
                      subtype-specific eRNAs on pathologic tissue samples. Thus,
                      this study provides proof-of-concept that subtype-specific
                      epigenetic changes relevant for PDAC progression can be
                      detected at a single-cell level in complex, heterogeneous,
                      primary tumor material.Subtype-specific enhancer activity
                      analysis via detection of eRNAs on a single-cell level in
                      patient material can be used as a potential tool for
                      treatment stratification.},
      keywords     = {Humans / Precision Medicine / Pancreatic Neoplasms:
                      pathology / Carcinoma, Pancreatic Ductal: pathology / RNA /
                      Gene Expression Regulation, Neoplastic / RNA (NLM
                      Chemicals)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37279184},
      doi          = {10.1158/1541-7786.MCR-22-0916},
      url          = {https://inrepo02.dkfz.de/record/282521},
}