Clonal Relatedness and Mutational Differences Between Upper Tract and Bladder Urothelial Carcinoma

To date, relatively few urothelial carcinomas of the upper tract (UTUC) have been examined using next-generation sequencing (NGS) methods. In this study, we sequenced 195 UTUC using a targeted NGS platform and compared the results to 454 urothelial carcinomas of the bladder (UCB). We identified significant differences in the prevalence of common genomic alterations between UTUC and UCB. Targeted NGS was a robust methodology for identifying UTUC patients whose tumors were microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR), the vast majority of which arose in patients with a pathogenic germline mutation in a Lynch syndrome-associated gene.

In individual patients with a history of both, we found that the UCB and UTUC were always clonally related. The latter results justify the development of methods to prevent lower tract seeding during surgery and the adoption of risk-adapted surveillance for bladder recurrence in patients with UTUC.

Written By: François Audenet, MD, Memorial Sloan Kettering Cancer Center, New York, New York

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