Molecular characterization of urothelial carcinoma of bladder and upper urinary tract.

Abstract

361 Background: It is a considerable unmet need to increase understanding of the molecular basis of urothelial carcinoma (UC) to refine the clinical decision-making process. We also aim to assess that whether we can apply similar principles in the management of upper tract UC (UTUC) based on the behavior of urinary bladder UC (UBUC). Methods: To study the molecular nature of UC, we performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes using the Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between UTUC and UBUC were compared. Results: Tumor samples from 34 UTUC and 63 UBUC patients were eligible for analyses. Two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was, although statistically insignificant, longer in UTUC than UBUC patients (59 vs. 41 months, P = 0.63). In total, we found 920 genetic alterations from 97 samples: most common type of somatic mutation was single nucleotide variants (SNVs; 494/525, 94.1%). After analyzing total genomic alteration frequency, we found that the frequency of CNVs was not significantly different between UTUC and UBUC group: most commonly observed mutation in the UBUC patients was TP53 (18.9%), followed by KDR (7.2%), FGFR3 (4.1%) and PIK3CA (4.1%). In the UTUC patients, TP53 (22.9%), KDR (6.5%), NOTCH1 (5.3%) and FGFR3 (4.1%) are most frequentl somatic mutations. We also identified five translocations in total UC cohort including one case with FGFR3–TACC3 (Chr4) fusion. Conclusions: Within the limitation of small sample size, we found no relevant differences in somatic mutation frequencies between UTUC and UBUC, indicating a basis for similar management strategies.