Synthetic lethal interactions with cancer CIN genes: investigating potential therapeutic targets

Genetic instability is a hallmark of cancer cells. One type of genomic instability seen in >80 percent of solid tumours is called Chromosome Instability (CIN). Cancer cells can contain mutations in CIN genes, and these genes make the cells more genetically susceptible to mutation than normal cells. Cells with CIN have large aberrations in chromosome structure and/or number, including the gain or loss of chromosomes and chromosomal breaks and fusions. This creates a vulnerability that can potentially be exploited therapeutically to selectively kill these cells. However, because of their nature, mutated CIN genes are difficult to identify directly.

Dr. Melanie Bailey is using RNA interference (RNAi) technology to specifically identify CIN genes of interest. She will be collaborating with Dr. Jason Moffat's laboratory at the University of Toronto to search for genes that pair with known CIN genes and are mutated in spontaneous and rare hereditary cancers. She will also be collaborating with Dr. Phil Hieter's lab at the University of British Columbia (UBC) to test a network of gene pairs previously identified by computer analysis of a public genetic database (BIOGRID) in a human cell line using RNAi.

By combining these approaches, Dr. Bailey expects to identify novel gene pairs that will be further studied using various cell biology and biochemical methods. She hopes that her research will help to better understand how CIN works and that it will provide insight into finding novel ways of killing CIN-mutated cells. Finally, Dr. Bailey will identify inhibitors of the CIN genes through collaboration with Dr. Michel Roberge, whose lab at UBC regularly screens chemical compounds for their inhibitory potential. These inhibitors may represent a viable cancer therapy for the future, as they would be specific for killing CIN-mutated cells.