Molecular pathology of urothelial carcinoma

The current personalized oncology era has witnessed significant efforts to integrate clinical, pathological, and molecular classifications. The growing need for molecular biomarkers to feed personalized oncology, together with the unprecedented wealth of knowledge on the molecular basis of bladder cancer, has led to a novel approach to this disease, incorporating molecularly generated data in clinical practice for locally advanced or metastatic disease. Translational research allows a better understanding of the early events in the development of urothelial carcinoma in the urinary bladder. Thus, mutations in the KMT2D and KDM6A chromatin-modifying genes confer competitive advantages that drive cells to colonize larger regions of the urothelium. Additional mutations in TP53, PIK3CA, FGFR3, or RB1 genes then trigger the process of malignant transformation in the urothelium. In the current review, we provide an overview of what could be the expected transition from the morphology-based classification to a combined, molecularly enriched reporting of clinically meaningful parameters aiming to promote personalized oncology of urothelial carcinoma. •Significant advances in bladder cancer genomics provide insights into tumorigenesis and cancer progression.•Chromatin modifying gene mutations, in particular, KMT2D and KDM6A confer advantages that drive the oncologic process.•Additional mutations in TP53, PIK3CA, FGFR3, or RB1 genes are the necessary step to trigger malignant transformation.•There is an expected transition from the morphology-based classification to a combined, molecularly enriched reporting.