The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

Abstract

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.

Keywords: bladder carcinoma; clonality; upper urinary tract carcinoma; urothelial carcinoma.

FIGURE 1

Assessment of the clonal relation of 15 primary UTUC and 19 subsequent UCBs based on (non)shared tumor‐specific genomic alterations between both entities detected by next‐generation sequencing. Additional transcriptomic profiling based on mRNAseq data is included for patients X, XI, XII and XIV (NU, normal ureteric tissue; UCB, urothelial carcinoma of the bladder; UTUC, upper urinary tract urothelial carcinoma) [Color figure can be viewed at wileyonlinelibrary.com]