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Core promoter mutation contributes to abnormal gene expression in bladder cancer

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Bladder cancer is one of the most mortal cancers. Bladder cancer has distinct gene expression signature, highlighting altered gene expression plays important roles in bladder cancer etiology. However, the mechanism for how the regulatory disorder causes the altered expression in bladder cancer remains elusive. | Huang et al. BMC Cancer 2022 22 68 https doi.org 10.1186 s12885-022-09178-z RESEARCH Open Access Core promoter mutation contributes to abnormal gene expression in bladder cancer Teng Huang Jiaheng Li and San Ming Wang Abstract Background Bladder cancer is one of the most mortal cancers. Bladder cancer has distinct gene expression signa- ture highlighting altered gene expression plays important roles in bladder cancer etiology. However the mechanism for how the regulatory disorder causes the altered expression in bladder cancer remains elusive. Core promoter con- trols transcriptional initiation. We hypothesized that mutation in core promoter abnormality could cause abnormal transcriptional initiation thereby the altered gene expression in bladder cancer. Methods In this study we performed a genome-wide characterization of core promoter mutation in 77 Spanish bladder cancer cases. Results We identified 69 recurrent somatic mutations in 61 core promoters of 62 genes and 28 recurrent germline mutations in 20 core promoters of 21 genes including TERT the only gene known with core promoter mutation in bladder cancer and many oncogenes and tumor suppressors. From the RNA-seq data from bladder cancer we observed altered expression of the core promoter-mutated genes. We further validated the effects of core promoter mutation on gene expression by using luciferase reporter gene assay. We also identified potential drugs targeting the core promoter-mutated genes. Conclusions Data from our study highlights that core promoter mutation contributes to bladder cancer develop- ment through altering gene expression. Keywords Bladder cancer Core promoter Gene expression Mutation Background for the genes related to cell cycle transcription and Bladder cancer is the tenth most common cancer world- cytoskeleton was well observed in bladder cancer 4 wide with an estimated 200 000 deaths per year 1 . Inci- mutation altering TERT expression was identified in dence rate of bladder cancer .