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We applied the evolutionary perspective to this study and found that chemotherapy acts as a selection pressure favoring the survival of some urothelial cancer cell clones. We identified striking heterogeneity between primary untreated and advanced chemotherapy-resistant tumors. The majority of the mutations were actually not shared between samples from, the same patient. As urothelial cancer progressed, developed new mutations that were different from those in the primary tumor. Surprisingly, this branching evolution was detected very early in the tumor’s lifetime. We also observed an enrichment of the APOBEC-induced mutational signatures in the post-chemotherapy tumors.
Our findings have important clinical implications. Most importantly, they show that tumor’s genetic testing at a single point in the tumor’s lifetime is only but a snapshot of a very complex evolutionary process. This becomes especially important as genomics makes further inroads into the clinical management of bladder cancer patients.
Read the Abstract
Author: Bishoy M. Faltas MD
Faltas B, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C, Rosenberg J, Mosquera JM, Robinson B, Elemento O, Sboner A, Beltran H, Demichelis F, Rubin MA. Clonal Evolution of Chemotherapy-resistant Urothelial Carcinoma. Nat Genet. 2016 Dec;48(12):1490-1499. doi: 10.1038/ng.369
Chemotherapy drives treatment resistance in bladder cancer https://meyercancer.weill.cornell.edu/news/2016-10-17/chemotherapy-drives-treatment-resistance-bladder-cancer