Research over the past decade has discovered a much broader array of alterations, including ERBB2, MDM2, CDKN2A, KDM6A, and ARID1A gene alterations in high-grade UC, key driver signaling pathways not previously recognized in low-grade UC (such as PIK3CA, STAG2, and RTK/RAS/RAF pathway genes), and gene expression differences across UC grades, stages, histology variants, and primary tumor locations [5,11,28,29,30]. The gene discussed is PIK3CA; the disease is neoplasm.