Jenny Giannopoulou, Prostate cancer methylome, fged_seattle_2013
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  • 1. Characterizing the prostate cancer methylome! Jenny Giannopoulou, PhD! Institute for Computational Biomedicine!
  • 2. Institute for Computational Biomedicine
 Weill Cornell Medical College, NY!
  • 3. Elemento lab
 http://physiology.med.cornell.edu/faculty/elemento/lab/! •  Regulatory networks in normal ! and malignant cells. ChIP-seq, ! RNA-seq, computational modeling ! to investigate how genes are! regulated in cancer cells! •  Cancer genomics and precision medicine! •  Epigenomics of cancer! Organizing “EpiWorkshops” ! https://sites.google.com/site/epiworkshop2013/!
  • 4. What?   Study genome-wide DNA methylation patterns in ! •  !localized PCa, ! •  !matched benign prostate tissue, as well as ! •  !CRPC (castration-resistant prostate cancer)! •  To understand how DNA methylation may contribute to PCa disease progression! •  To distinguish indolent PCa from more advanced forms! Why?  
  • 5. How?   !RRBS: Reduced Representation Bisulfite Sequencing  a high-coverage single-base resolution DNA methylation method PLoS Genet. 2012;8(6):e1002781. Epub 2012 Jun 21.! • ! Localized PCa (7) Berger MF et al. Nature. 2011 Feb 10;470(7333):214-20! • ! Matched benign prostate tissues (7)! • ! CRPC/Neuroendocrine PCa (6) Beltran H et al. Cancer Discov. 2011 Nov; 1(6):487-495.! Apply  RRBS  on  20  cases   RRBS data available at GEO: GSE41701!
  • 6. Overall increased DNA methylation in PCa, 
 consistent across cases

  • 7. Differentially methylated regions (DMRs) regions containing at least five differentially methylated CpGs! Negative correlation between DNA meth ! and gene expression! Heterogeneous methylation levels in PCa! Hyper DMRs in Promoters – Hypo in Interenic/Introns!
  • 8. EGR1 may play a role in PCa disease progression!
  • 9. DNA methylation at CGIs increases with disease severity!
  • 10. CGIs with systematic increase of methylation between benign, PCa, and CRPC!
  • 11. DNA methylation may predict disease severity!
  • 12. Dept. of Physiology and Biophysics! Institute for Computational Biology! Weill Cornell Medical College! –  Jenny Giannopoulou! –  Olivier Elemento! –  Andrea Sboner ! Dept. of Pathology and Laboratory Medicine! Weill Cornell Medical College! –  Mark Rubin! –  Pei-Chun Lin! –  Kyung Park! –  Juan Miguel Mosquera! Dept. of Medicine, Hematology Oncology Division! Weill Cornell Medical College! –  Himisha Beltran! Dept. of Urology and the LeFrak Center for Robotic Surgery! Weill Cornell Medical College! –  Ashutosh K. Tewari! Broad Institute of Harvard and MIT! Dept. of Medical Oncology, Dana Farber Cancer Institute! –  Levi Garraway! Collaborators!
  • 13. Thank you! http://physiology.med.cornell.edu/faculty/elemento/lab/jenny! http://icb.med.cornell.edu/wiki/index.php/Elementolab/! @jgiannopoulou! @Elementolab!