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Developments in the area of bladder cancer genomics and its importance in the treatment selection

Jyoti Sharma, Barnali Deb, Prashant Kumar*

With the advent of next-generation sequencing technologies, tremendous progress has been made in the understanding of the genomic landscape of several tumor types. Clinicopathologically bladder carcinoma is classified into non-muscle invasive bladder cancer and muscle invasive bladder cancer. Patients are often diagnosed with bladder carcinoma at an advanced stage, owing to a lack of early clinical symptoms and effective biomarkers for early detection. Failure of chemoradiotherapy at an advanced stage usually results in a poor outcome. Currently, there are limited targeted therapies available for bladder carcinoma. Thus, there is an immediate need to identify alternative strategies and novel therapeutic targets for the treatment of bladder carcinoma. The genomic underpinnings of bladder carcinoma may lead to the better understanding of this disease and improved targeted therapy. A large number of genomic alterations including somatic mutations, copy number alterations and fusion genes were identified to be involved in the pathogenesis of bladder carcinoma. A high mutational burden was observed in bladder carcinoma as compared to other tumors. Recurrent somatic mutations in genes such as TP53, KMT2D, RB1, FGFR3, KDM6A, STAG2 and PIK3CA were identified. Multiple signaling pathways such as the cell cycle pathway, DNA repair pathway, chromatin remodeling and histone modifications were found to be altered. Most likely, targeting mutated genes of these altered pathways could provide opportunities for personalization of bladder carcinoma therapy. This review discusses the molecular alterations, altered identified genes and the molecular pathways involved in bladder carcinoma.