I4C Epigenetics Working Group
description
Transcript of I4C Epigenetics Working Group
I4C Epigenetics Working Group
Barcelona, September 2011
Proposal
• Exploratory section: An epigenetic signature of childhood cancer obtained at birth
• Screening section: An epigenetic signature of cancer predisposition linked to high birth weight
Objectives
• To define an epigenetic signature of risk of childhood leukemia in blood obtained at birth.
• To discover an epigenetic signature of cancer risk in blood obtained from high birth weight babies.
Hypothesis
Environmental exposure during early embryonic life is able to imprint an epigenetic signature that can be used as a biomarker of exposure and susceptibility to cancer
Why Epigenetics?
Why Epigenetics?
• Translocations frequently target epigenetic mechanisms
• DNA methylation marks are commonly deregulated in ALL
• Hot spots for translocations are common in CpG-rich regions
Why Epigenetics?
• Translocations frequently target epigenetic mechanisms
Translocations frequently target chromatin modifiers
MLLCBPMOZMORFp300
Fusion proteins are involved in the recruitment of silencing complexes
HDACsDNMTsNCOR1NCOR2
Why Epigenetics?
• DNA methylation marks are commonly deregulated in ALL
DNA methylation is deregulated in ALL
MDR1, THSBS2, THSBS1, MYF3, ER, P15, CD10, c-ABL, p16, and p73
overrepresentation of Wnt-related genes
Why Epigenetics?
• Hot spots for translocations are common in CpG-rich regions
Tsai et al, Human Chromosomal Translocations at CpG sites and a Theoretical Basis of their Lineage and Stage Specificity. Cell 2008
birth
ALL
Approach
• 200 archived blood spots (stratified according to birth weight)
• DNA extraction, bisulfite modification, whole genome amplification
• Epigenome analyses: Infinium 450K
• Bioinformatics: epigenetic signature of high birth weight
• Validation / Replication
Perspectives• this proof of principle approach will provide
a starting point from which to explore the association of multiple environmental exposures to an epigenetic profile linked to childhood cancer
• the identification of reversible epigenetic alterations associated with environmental cues may have a strong impact in understanding and preventing cancer
The I4C Epigenetics Working GroupJia Chen
Mount Sinai School of Medicine
Jeff Craig
Murdoch Children’s Research Institute
Terence Dwyer
Murdoch Children’s Research Institute
Zdenko Herceg
International Agency for Research on Cancer
Hector Hernandez-Vargas
International Agency for Research on Cancer
Rayjean J. Hung
University of Toronto
Yoshimi Inaba
Murdoch Children’s Research Institute
Carol H. Kasten
National Children’s Study
Sharon Savage
National Cancer Institute
Camilla StoltenbergNorwegian Institute of Public Health Gabriella TikellisMurdoch Children's Research Institute
Joseph L. WiemelsUniversity of California, San Francisco Nicholas C. WongMurdoch Children's Research Institute