Mapping the Cellular Landscape
Understanding how epigenetics influences cancer
June 1, 2015
While cancer has been long viewed as a genetic disease, researchers are discovering that epigenetics – the biological mechanisms that turn genes on or off – also plays a role. The human genome – the entire DNA content of a cell – remains essentially unchanged and is the same throughout the body. Conversely, the epigenome – the chemical compounds that modify, or mark, the genome – evolves over the course of a person's life and can vary from cell to cell. "To understand epigenetic influences on disease, we need to know how a ‘normal' epigenome would function," says Dr. Martin Hirst of the BC Cancer Research Centre. "And while we can define a cell by its epigenome, there are hundreds of distinct cell types so it's a significant undertaking to complete the picture."
As a member of the International Human Epigenomic Consortium (IHEC), the BC Cancer Research Centre and the University of British Columbia are collaborating with several other partners to create a "reference map" for human cell types. Since the epigenome changes as cells age and in response to environmental influences, researchers are generating multiple reference maps for each cell type. The goal is for partners to develop an open access database of 1,000 reference epigenomes based on standards set by IHEC. With support from clinicians who provide high quality human tissue, the Centre is generating maps of normal and malignant cells related to cancers in the brain, colon and breast, among others. To date, with funding from CIHR, the Centre has profiled 38 cell types, making it on track to reach its goal of 100. "Even now, the project is providing critical references for normal cells that we can compare against disease," says Dr. Hirst. "For example, we're using data we've generated to understand the epigenetic landscape of normal human breast cell types as a foundation to understand breast cancer."
Gascard, P. et al. (in review). Epigenetic and transcriptional determinants of the human breast.
Kundaje, A. et al. (in press). Integrative analysis of 111 reference human epigenomes.
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