Medicine and Health Sciences Commons^™

Changing Selection And Epistasis On Drivers Over Tumorigenesis In Primary And Metastatic Prostate Cancer, Alexander Yang

Yale Medicine Thesis Digital Library

Background: Many attempts have been made to characterize and describe the driver genes and mutations responsible for prostate cancer tumorigenesis. We have quantified the cancer effect size—a direct measurement of the survival advantage a mutation confers—for 2699 primary and metastatic prostate tumor samples. Our measure of cancer effect treats tumorigenesis as an evolutionary process, subject to positive and negative selective pressures. We have applied this metric in a stage-specific manner to elucidate which mutations are selected for as prostate cancer develops.Methods: We analyzed 2699 prostate cancer tumor exomes, genomes, and panel sequences (1648 primary tumors and 1051 metastatic samples). The …