Ashton Omdahl; Shun Sambongi; Megan Major; Emily LeBaron; Dallas Larsen; Daniel Lewis, Brigham Young University
In the ongoing effort to improve clinical diagnosis and treatment for breast cancer patients, understanding tumor heterogeneity remains a focal point of medical research. While individual gene aberrations or mutations have been identified as indicators of breast cancer prognostic outcomes, research in head and neck squamous cell carcinoma has revealed that paired genetic mutation events can be associated with decreased patient survival. We set out to identify such paired genetic mutation events associated with prognostic outcomes in breast cancer patients. Using somatic mutation, chromosomal aberration, and clinical patient data available online via The Cancer Genome Atlas, we performed Cox proportional hazards-ratio analysis on 50 prognostic event pairs of single nucleotide polymorphisms (SNP) and copy number variants (CNV) across 897 patients. Resulting hazards ratio scores indicate the effect of variables on patient life expectancy, with values greater than 1 indicating a decrease in patient life expectancy. Preliminary work has revealed a meaningful decrease in survival probability in patients with both the PIK3CA SNP and BRIP1 CNV, with a hazard ratio score of 1.85. PIK3 pathway mutations are frequently associated with breast cancer tumorigenesis, and BRIP1 aberrations may interfere with BRCA1-interacting helicase, suggesting a possible role in breast cancer tumorigenesis. Interestingly, CNV events paired with mutation events in the tumor-suppressing TP53 gene do not appear to experience the same decrease in survival probability. We continue to investigate these prognostic indicators, possible recorded mechanisms in the literature, and present our findings.