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@ARTICLE{KimWanner:154460,
      author       = {S.-Z. Kim-Wanner$^*$ and Y. Assenov$^*$ and M. B. Nair$^*$
                      and D. Weichenhan$^*$ and A. Benner$^*$ and N. Becker$^*$
                      and K. Landwehr and R. Kuner$^*$ and H. Sültmann$^*$ and M.
                      Esteller and I. Koch and M. Lindner and M. Meister and M.
                      Thomas and M. Bieg$^*$ and U. Klingmueller$^*$ and M.
                      Schlesner$^*$ and A. Warth and B. Brors$^*$ and E. Seifried
                      and H. Bonig and C. Plass$^*$ and A. Risch$^*$ and T. Muley},
      title        = {{G}enome-wide {DNA} methylation profiling in early stage
                      {I} lung adenocarcinoma reveals predictive aberrant
                      methylation in the promoter region of the long non-coding
                      {RNA} {PLUT} - an exploratory study.},
      journal      = {Journal of thoracic oncology},
      volume       = {15},
      number       = {8},
      issn         = {1556-0864},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2020-00782},
      pages        = {1338-1350},
      year         = {2020},
      note         = {2020 Aug;15(8):1338-1350#EA:B370#},
      abstract     = {Surgery is the treatment of choice in early stage I lung
                      adenocarcinoma. However, a considerable portion of patients
                      experience recurrence within the first two years following
                      complete resection. Especially suitable prognostic
                      biomarkers are not available that identify patients at high
                      risk for recurrence who may probably benefit from adjuvant
                      treatment. This study aimed to identify methylation markers
                      for early recurrence that may become important tools for the
                      development of new treatment modalities.Genome-wide DNA
                      methylation profiling was performed on 30 stage I lung
                      adenocarcinomas comparing 14 patients with early metastatic
                      recurrence to 16 patients with a long-term relapse-free
                      survival period using methylated-CpG-immunoprecipitation
                      (MCIp) followed by high-throughput next generation
                      sequencing. The differentially methylated regions (DMRs)
                      between the two subgroups were validated for their
                      prognostic value in two independent cohorts using the
                      MassCleave Assay, a high-resolution quantitative methylation
                      analysis.Unsupervised clustering of patients in the
                      discovery cohort based on DMRs identified patients with
                      shorter relapse free survival (HR 2.23; $95\%$ CI 0.66 to
                      7.53; p=0.03). In two validation cohorts promoter
                      hypermethylation of the long non-coding RNA (lncRNA) PLUT
                      was significantly associated with shorter relapse free
                      survival (HR 0.54; $95\%$ CI 0.31 to 0.93; p<0.026) and
                      could be shown to be an independent prognostic factor in the
                      multivariate cox regression analysis.Promoter
                      hypermethylation of the lncRNA PLUT is predictive in
                      patients with early stage I adenocarcinoma at high risk for
                      early recurrence. Further studies are needed to validate its
                      role in carcinogenesis and its use as a biomarker to
                      facilitate patient selection and risk stratification.},
      cin          = {B370 / C060 / B063 / HD01 / FM01 / B080 / B200 / B330},
      ddc          = {610},
      cid          = {I:(DE-He78)B370-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B063-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)FM01-20160331 / I:(DE-He78)B080-20160331 /
                      I:(DE-He78)B200-20160331 / I:(DE-He78)B330-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32272161},
      doi          = {10.1016/j.jtho.2020.03.023},
      url          = {https://inrepo02.dkfz.de/record/154460},
}