EUO Collaborative Review – Priority ArticleEditorial by Rohit K. Jain, Jeffery S. Ross, Andrea Necchi and Philippe E. Spiess on pp. 180–181 of this issueGenetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy
Introduction
Urothelial carcinoma (UC), which encompasses disease of the bladder (90–95%) and renal pelvis/ureter (ie, upper tract urothelial carcinoma [UTUC]; 5–10%), is the sixth most common cancer in the USA [1], [2]. Historically, these two diseases have been grouped together because of their histologically similar appearance. Clinically, UTUC and bladder carcinoma have different embryologic precursors and have different responses to therapy, leading many to believe that they should be considered as distinct entities [3]. Recent advancements in technology have led to a better genomic understanding of both bladder cancer and UTUC. Comparisons between tumor mutational burden (TMB) and expression profiles between bladder cancer and UTUC have now shed light on the genomic differences between the two entities [4], [5], [6], [7], [8]. Understanding these differences will be very important for future therapeutic considerations, especially in clinical trial design.
Section snippets
Evidence acquisition
Eligible articles were identified through searches of the electronic databases, Cochrane and Web of Science. English-language articles published between January 2000 and February 2020 were identified and included. The keywords used in the search included the following: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics. Additional informative articles were collected by cross-referencing the bibliography of previously selected articles. The article
Genetic alterations in UTUC
The first mutational analysis of UTUC was from a targeted whole-exome analysis of 83 tumor samples from the Memorial Sloan Kettering Cancer Center (MSKCC) with a more recent updated analysis of 195 UTUC tumors [6], [9]. The most frequently mutated genes were FGFR3 (40%), KMT2D (37%), KDM6A (32%), TP53 (26%), and ARID1A (23%) [9]. Most FGFR3 mutations were missense (putative driver) mutations, while KTMT2D, KDM6A TP53, and ARID1A were truncating or missense (putative passenger) mutations [9]. In
Conclusions
The improved genomic understanding of bladder UC and UTUC has shed light onto novel pathways for therapeutic targeting. Furthermore, it has allowed for the ability to identify biomarkers for response. While bladder cancer and UTUC share similarities, to improve treatment outcomes, we need to better functionalize genomics into therapeutics; while this has not yet occurred, we appear to be on the cusp of such.
Author contributions: John P. Sfakianos had full access to all the data in the study and
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