Characterizing the prostate cancer methylome.

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!

13. 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!

14. Thank you!
http://physiology.med.cornell.edu/faculty/elemento/lab/jenny!
http://icb.med.cornell.edu/wiki/index.php/Elementolab/!
@jgiannopoulou!
@Elementolab!