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The Landscape of Prostate Tumour Methylation - PubMed

4 hours ago
  • #Prostate Cancer
  • #Epigenomics
  • #DNA Methylation
  • Prostate cancer exhibits significant clinical and molecular heterogeneity, with epigenomic aspects less understood than genomic ones.
  • A compendium of 3,001 multi-ancestry prostate methylomes was created, covering normal tissue to poly-metastatic disease, with 884 samples having multi-omic DNA/RNA data.
  • Four epigenomic subtypes were identified that risk-stratify patients and reflect distinct evolutionary trajectories.
  • Extensive regulatory interplay exists between DNA copy number and methylation, with transcriptional consequences varying across genes and disease stages.
  • Epigenetic dysregulation signatures for 15 clinico-molecular features were defined, enabling predictive models for each, including features that predict patient outcome and synergize with clinical prognostic factors.
  • The study reveals a complex interplay between tumour genetics and epigenetics that modifies gene-expression programs and clinical presentation, partly through epigenetic aging modulation.