PP159 Differences in unique molecular characteristics of bladder cancer and upper tract urothelial carcinoma in Korean patients from the K-MASTER project

Urothelial carcinoma differs in response to treatment and prognosis depending on the site of occurrence. This may be due to the unique biodiversity of the site of origin. This study aimed to compare the genomic properties of bladder cancer (BC) and upper tract urothelial carcinoma (UTUC) using the next-generation sequencing (NGS) of K-MASTER project in Korea. This study included patients with unresectable or metastatic UC (bladder, ureter, renal pelvis), who were enrolled in the K-MASTER screening system between Jun 2017 and Jul 2021. Molecular profiling was performed on tumor tissue with the K-MASTER NGS panel. Our study included 231 patients (175 BC and 56 UTUC). In the BC group, there were 148 men and 27 women, whereas 40 men and 16 women in the UTUC group. In the whole, median number of variants per sample was 11. C to T (C>T) substitutions were the dominant mutation type in both BC and UTUC. There was a marked difference of between molecular characteristics of BC and UTUC. The most frequently mutated genes were TP53 (48%), KMT2D (30%), ARID1A (22%), ATM (20%) and ERCC2 (17%) in BC, whereas KMT2D (63%), TP53 (59%), BRCA2 (24%), CREBBP (24%) LRP1B (17%) were most frequently observed in UTUC. Restricting only those that were statistically significant (p < 0.05), the genomic alterations observed more frequently in UTUC than in BC were BRIP1 (Odds ratio, OR 0.142), FLT3 (OR 0.18), CDH5 (OR 0.152), BCORL1 (OR 0.327), and FANCL (0.103), whereas ERCC2 (OR 4.903) and ERBB2 were observed more frequently in BC. Interestingly, our data differed significantly from the TCGA data. TP53 (59%, 22%) was more observed and FGFR3 (18%, 46%) was less observed in our UTUC cohort compared to TCGA UTUC cohort. There was no significant difference of signaling pathway alterations between the TCGA data and our data. However, the cell cycle and TP53 pathway (71.4%, 73.2%) were found to be higher in our UTUC, whereas the RTK-RAS pathway accounted for 76.5% in TCGA UTUC, showing a significant difference. In mutational signature analysis, Signature 3 (DNA double-strand break) was highly dominant in both BC and UTUC. Signature 13 (activity of APOBEC Cytidine Deaminase) was mainly observed in BC, while Signature 18 (damage by reactive oxygen species) was mainly observed in UTUC. This study showed significant differences in genomic properties between BC and UTUC. It has been confirmed that there are unique characteristics depending on race. These results imply that it is necessary to comprehensively understand the unique genomic characteristics in treating Korean BC and UTUC.