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@ARTICLE{Craddock:305205,
      author       = {J. Craddock and P. Lutsik$^*$ and P. X. Y. Soh and M. Louw
                      and M. M. Hasan and S. M. Patrick and S. B. A. Mutambirwa
                      and P. D. Stricker and H. E. A. Förtsch and M. S. R.
                      Bornman and C. Gerhäuser$^*$ and V. M. Hayes},
      collaboration = {H. P. Africa1K},
      othercontributors = {G. S. Prins and P. M. Ngugi and W. Jaratlerdsiri and W. M.
                          Ombuki and D. M. Moreira and I. C. Madueke and M. T. Lebelo
                          and T. M. N. Mbeki and M. Obida and M. Obida and R. A.
                          Campbell and M. B. Radzuma and G. Stellmacher and J.
                          Gamxamub and R. M. J. Menoe and J. Jiang and T. Gong and K.
                          Uthayopas and K. Gheybi and R. Huang and K. Zhou and U.
                          Maendo and M. Loda and G. N. Fanelli and D. C. Wedge and A.
                          Tapinos and V. Holmes and R. G. Bristow and D. S. Brewer and
                          A. Gihawi and C. S. Cooper and R. A. Eeles and Z. Kote-Jarai
                          and M. Argos and I. Barnhoorn and L. Birch and M. E. Nyaga
                          and M. O. Oyaro and J. Shirinde and D. I. Walker and E. O.
                          O. Walong and G. S. Wanjiku and M. Quaid},
      title        = {{M}ethylation reprogramming associated with aggressive
                      prostate cancer and ancestral disparities.},
      journal      = {Molecular systems biology},
      volume       = {21},
      number       = {12},
      issn         = {1744-4292},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2025-02053},
      pages        = {1676-1701},
      year         = {2025},
      note         = {2025 Dec;21(12):1676-1701},
      abstract     = {African men are disproportionately impacted by aggressive
                      prostate cancer (PCa). The key to this disparity is both
                      genetic and environmental factors, alluding to epigenetic
                      modifications. However, African-inclusive prostate tumour
                      DNA methylation studies are lacking. Assembling a
                      multi-geo-ancestral prostate tissue cohort, including men
                      with (57 African, 48 European, 23 Asian) or without (65
                      African) PCa, we interrogate for genome-wide differential
                      methylation. Overall, methylation appears to be driven by
                      ancestry over geography (152 southern Africa, 41 Australia).
                      African tumours show substantial heterogeneity, with
                      universal hypermethylation indicating more pervasive
                      epigenetic silencing, encompassing PCa suppressor genes and
                      enhancer-targeted binding motifs. Conversely, African
                      tumour-associated heterochromatic hypomethylation suggests
                      chromatin relaxation and developmental pathway activation
                      via enhancer targets. Notably, non-prostate lineage elements
                      appeared preferentially exploited in African tumorigenesis,
                      with ancestry potentially influencing the extent of
                      lineage-inappropriate activation, and tumour progression
                      marked by repression of developmental regulators. Together,
                      these findings point to extensive epigenetic plasticity in
                      African tumours, with intergenic regulatory remodelling
                      promoting genomic instability, metastatic potential and
                      aggressive disease phenotypes.},
      keywords     = {African Ancestry (Other) / Differential Methylation (Other)
                      / Health Disparity (Other) / Prostate Tumours (Other)},
      cin          = {B370},
      ddc          = {570},
      cid          = {I:(DE-He78)B370-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41057544},
      doi          = {10.1038/s44320-025-00153-x},
      url          = {https://inrepo02.dkfz.de/record/305205},
}