It is profound that despite years of intensive therapeutic efforts, a staggering 50-60% of patients with muscle-invasive urothelial bladder cancer will have a local or distant disease recurrence within five years with only limited therapeutic options. Therefore, it is imperative to understand how these tumors develop and continue efforts to identify new therapeutic targets. Because basal and luminal tumor subtypes of invasive bladder tumors have significant prognostic and predictive impacts for patients we sought to answer the question: When does subtype commitment occur and which signaling gene pathways are important during the process of tumorigenesis?