HRAS and urothelial hyperplasia: Mutations in HRAS are primarily associated with non-muscle-invasive urothelial carcinoma and transgenic mouse models have demonstrated evolution of urothelial hyperplasia to low-grade non-invasive papillary tumors.[37, 38] Therefore, overexpression of activated HRAS is sufficient to induce urothelial tumorigenesis and the receptor tyrosine kinase – Ras pathway contributes to the low-grade non-invasive papillary pathway of urothelial tumorigenesis.