Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Pathology
Supervisor
Dr. Joan H.M. Knoll
Second Advisor
Dr. Peter K. Rogan
Third Advisor
Dr. Ann F. Chambers
Abstract
Cancer genomes accumulate chromosomal abnormalities and gene mutations but must maintain the ability to survive in vitro. We sought evidence in breast cancer that genetic selection acts to maintain tumour survival. Analysis of genomes from 243 breast tumours revealed 766 unstable and 812 stable contiguous genomic regions. Stable DNA targets were confirmed by quantitative PCR in six breast cancer cell lines. Stable regions contained 9,463 protein coding genes, of which expression of 7,489 were analyzed. We found 78% (5804/7489) of genes had both stable copy number and expression. The breast cancer genome preferentially preserves functions that include cellular metabolic processes, gene expression regulation, DNA packaging, cellular component assembly, RNA metabolism and regulation of apoptosis. Stable genes were consistently found to be targets of therapeutic drugs. Conservation of this minimal gene set may explain the effectiveness of certain chemotherapeutic agents that act on multiple gene products in this set.
Recommended Citation
Park, Nicole I., "TOWARDS AN UNDERSTANDING OF GENETIC SELECTION IN BREAST CANCER" (2010). Digitized Theses. 4550.
https://ir.lib.uwo.ca/digitizedtheses/4550