biostudies-literatureAnurag MNCI NIH HHS109179https://www.ebi.ac.uk/biostudies/studies/S-EPMC10910238biostudies-literatureUnknown27(3)Urothelial carcinoma <i>in situ</i> (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors. We identified a 46-gene expression signature in CIS samples including selectively upregulated known druggable targets <i>MTOR</i>, <i>TYK2</i>, <i>AXIN1</i>, <i>CPT1B</i>, <i>GAK</i>, and <i>PIEZO1</i> and selectively downregulated <i>BRD2</i> and <i>NDUFB2</i>. High expression of selected genes was significantly associated with CIS in an independent dataset. Mutation analysis of matched CIS and papillary tumors revealed shared mutations between samples acroiScienceMultiomics profiling of urothelial carcinoma <i>in situ</i> reveals CIS-specific gene signature and immune characteristics.PMC10910238P30 CA008748P50 CA221745Strandgaard TDou YAl-Ahmadie HNordentoft IKim SHJensen JBTaber AInman BAComperat EAnurag MDyrskjot LLerner SPfalseMultiomics profiling of urothelial carcinoma <i>in situ</i> reveals CIS-specific gene signature and immune characteristics.Urothelial carcinoma <i>in situ</i> (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors. We identified a 46-gene expression signature in CIS samples including selectively upregulated known druggable targets <i>MTOR</i>, <i>TYK2</i>, <i>AXIN1</i>, <i>CPT1B</i>, <i>GAK</i>, and <i>PIEZO1</i> and selectively downregulated <i>BRD2</i> and <i>NDUFB2</i>. High expression of selected genes was significantly associated with CIS in an independent dataset. Mutation analysis of matched CIS and papillary tumors revealed shared mutations between samples acro2024-01-01T00:00:00Z2024 Mar2026-06-02T21:17:39.516Z2025-04-19T22:00:57.484ZS-EPMC109102383843996110.1016/j.isci.2024.109179