Mutational landscape of non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer (NMIBC) includes stage Ta and stage T1 tumors and carcinoma in situ (CIS). Grading of Ta tumors sub-divides these lesions into papillary urothelial neoplasms of low malignant potential (PUNLMP) and low- and high-grade non-invasive papillary urothelial carcinoma [1]. CIS is by definition high-grade and the majority of stage T1 tumors are of high-grade. This pathologic heterogeneity is associated with divergent clinical outcome, with significantly worse prognosis for patients with T1 tumors or CIS. A wealth of molecular information has accumulated on NMIBC including mutational data that ranges from the whole chromosome level to next generation sequence data at nucleotide level. This has not only identified key genes that are mutated in NMIBC, but also provides insight into the processes that shape their mutational landscape. Although molecular analyses cannot yet provide definitive personal prognostic information, many differences between these entities promise improved disease management in the future. Most information is available for Ta and T1 samples and this is the focus of this review.