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|
Canada's Michael Smith Genome Sciences Centre
National Cancer Institute of Canada
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.
For all project related inquires please contact us.
Sherry Wang, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604-707-5900 x 54491