Molecular and Clinical Insights into the Role and Significance of Mutated DNA Repair Genes in Bladder Cancer

Philip H Abbosh, Elizabeth R Plimack, Philip H Abbosh, Elizabeth R Plimack

Abstract

DNA damage response and repair genes (DDR genes) are commonly mutated in bladder cancer. The biological impact of these mutations is an area of intense basic, translational, and clinical interest. As next generation sequencing increases its foothold in the treatment of localized and advanced bladder cancer, the role of DDR genes will continue to evolve. We review the inventory and biology of DDR genes in bladder cancer and describe known and candidate roles for loss of DDR genes to engender therapeutic susceptibilities to various anti-cancer agents.

Keywords: DNA damage response/repair; bladder cancer; chemoresponse; cisplatin; immunotherapy; upper tract urothelial carcinoma.

Figures

Fig.1
Fig.1
A Mutations in DDR genes occurring the TCGA BLCA data set (n = 130). Note that only cases with variants present are depicted. Figures were generated using Cbioportal [62, 63].
Fig.2
Fig.2
Copy number alterations in DDR genes occurring in the TCGA BLCA data set (n = 408). Note that only cases with variants present are depicted. Figures were generated using Cbioportal [62, 63].
Fig.3
Fig.3
Pan-cancer analysis of mutations in DDR genes listed in Fig. 1 as described in >10,000 tumors using MSK-IMPACT. Figures were generated using Cbioportal [62, 63].

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