Mutational signature and prognosis in adenocarcinoma of bladder.

Abstract

655 Background: Adenocarcinoma of bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here we aim to reveal mutational and transcriptomic landscapes of adenocarcinoma of bladder and their relationship with prognosis. Methods: Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of bladder were included. These included 16 patients with primary bladder adenocarcinomas and 7 patients with urachal adenocarcinoma. Whole exome sequencing, whole genome sequencing, bulk RNA-Seq and single-cell RNA-Seq were conducted for the specimens. Correlation analysis, survival analysis and t tests were also performed. Results: Prevalent T>A substitutions were observed among somatic mutations, and major tri-nucleotide contexts included 5′-CTC-3′and 5′-CTG-3′. This pattern was mainly contributed by COSMIC Signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes also enriched KEGG term “chemical carcinogenesis”. Transcriptomic analysis implied high immune infiltration and luminal-like feature in majority of samples. Interestingly, a small fraction of samples with APOBEC-derived mutational signature exhibited higher risk of disease progression compared with samples with only chemical carcinogen-related signature, confirming molecular and prognosis heterogeneity in bladder adenocarcinoma. Conclusions: This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and chemical carcinogen-related mutational signature indicates good prognosis in adenocarcinoma of bladder.