Abstract IA002: Molecular subtypes of NMIBC

Abstract Non-muscle-invasive bladder cancers (NMIBCs) show large variation in disease aggressiveness which is not fully explained by differences in clinical and pathological factors. It is therefore essential to increase our understanding of the molecular landscape of NMIBC to improve risk assessment and identify potential therapeutic targets. In 2021, we published the four transcriptomic UROMOL2021 classes of NMIBC: class 1, class 2a, class 2b and class 3 (Lindskrog et al. , Nature Communications, 2021). Multiple other subtyping schemes for NMIBC have been published, including, among others, the Lund taxonomy (Marzouka et al. , The Journal of Molecular Diagnostics, 2022), the stage-stratified subtypes from Leeds (Hurst et al. , Cell Reports Medicine, 2021) and BRS1-3 from Rotterdam (de Jong et al. , Science Translational Medicine, 2023). In my presentation, I will give an overview of the development and status of NMIBC subtypes and discuss clinical utility. Furthermore, I will present novel data from the UROMOL cohort, where we have now performed a comprehensive genomic characterization of tumors using whole exome sequencing (n=438) and shallow whole genome sequencing (n=362). Overall, we observe a large genomic variation within NMIBC that is associated with different gene expression profiles (UROMOL2021 classes). We performed integrative clustering analysis of somatic mutations, copy number alterations and gene expression data for 230 tumors and identified four “iClusters”, which were highly prognostic and went beyond the single-layer stratifications of tumors. Multi-omics subtyping may improve our understanding of differences in disease aggressiveness within NMIBC further, which could ultimately be used to improve risk assessment of patients and identify potential therapeutic targets. Citation Format: Sia V. Lindskrog. Molecular subtypes of NMIBC abstract. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30 (10Suppl): Abstract nr IA002.