The identification of mutation specific inhibitors through whole genome re-sequencing of breast cancer cell-lines
To use next generation sequencing technology to derive the complete genomic sequence of breast cancer cell lines.
| Project Leaders |
Steven Jones
|
|---|---|
| Project Co-Investigators |
Angela Brooks-Wilson
Jianghong An |
| Involved Organizations |
Canada's Michael Smith Genome Sciences Centre
|
| Funding Agencies |
National Cancer Institute of Canada
|
Overview
We will use nascent next-generation
sequencing technology to derive the complete genomic sequence of breast cancer
cell lines.
The Illumina 1G next generation sequencing
technology allows the derivation of over one billion bases of DNA sequence information
in a single machine run. Although these reads are short, 25 to 40 base pairs,
they allow polymorphisms and rearrangement breakpoints to be mapped against a
reference genome, essentially allowing the complete sequence to be inferred.
The Genome Sciences Centre has already developed expertise in both laboratory
and bioinformatic aspects of running this machine.
Software has been developed to map single
nucleotide polymorphisms to the reference genome; however software to map
deletion and rearrangement events, which are common in cancer, will need to be
developed as part of this program.
This study will not only determine all the
protein coding changes which have occurred within the cell lines but also for
the first time allow potential changes in regulatory elements to also be
determined. We are well placed to undertake such analysis having already
developed the CisRED (http://www.cisred.org/), computationally detected
regulatory element database as well as the OregAnno (http://www.oreganno.org/ ) database of
known regulatory elements and their polymorphisms.
Once detected, we will assess mutations
bioinformatically for their potential as therapeutic targets. In-silico molecular docking using the ICM software from MolSoft
will be used to screen known drug and compound databases and the ability of
these compounds to inhibit growth will be assessed experimentally.
Contact Information
For all project related inquires please contact us.Cynthia Ferguson, Project Manager
Genome Sciences Centre, BC Cancer Agency
Email: cferguson@bcgsc.ca
Phone: 604-707-5900 x 6081
Fax: 604-876-3561