Daniel De Carvalho

Daniel De Carvalho (University Health Network / University of Toronto, Canada)
“Translational Aspects of DNA Methylation in Cancer”

  • [DNA Methylation patterns are tissue specific and conserved across individuals]
  • Deconvoluting the tumor microenvironment from DNA methylation data CYBERSORT to profile TME TILS
  • DNA methylation patterns are reprogrammed in cancer patients but retain tissue-specificitcirculating cell-free DNA (cfDNA)
  • [Cancer Cell 2014 Hoadly. ]
  • Detection f ctDNA is a function of ctDNA abundance, sequencing depth and number of features investigated. (Shen et al submitted)
  • Our solution -> capture-based approach
  • Antibody IP + filler DNA
  • cfMeDIP-seq in cell line DNA
  • Thousands of DMRs
  • Pancreatic cancer samples (n=400 in validation cohort)
  • CfDNA methylation profile matches tumor profile 
  • Hoadley et al Cancer Cell 2014. Reprogramming of Methylation in cancer
  • Classifier trained in the TCGA data
  • CfMeDIP-seq can discriminate different cancer sub-types

  • Epigenetic s
    • Genome-wide DNA methylation profiling highly informative of cancer type and Gussie of origin of cfDNA
    • High sensitive and specificity
    • Cost-effect
  • Machine learning (classifier)
    • Robust and accurate
    • Performance is continually improved

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