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Identification of the gene expression changes and gene regulatory aspects in ELF3 mutant bladder cancer

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Abstract

Background

Recent genome-wide studies revealed the molecular subtypes and mutational landscape of bladder cancer, which is the 10th most common cancer causing many deaths. ELF3 is one of the frequently mutated genes in bladder cancer with 14% alteration rate. It mainly functions as an epithelial transcription factor and its proper function is critical for the urothelium development. However, the impact of ELF3 mutations in bladder cancer is currently unknown.

Methods and results

In this study, we analysed the gene expression data available for primary bladder cancer and bladder cancer cell lines according to the mutation status of ELF3. Our results show that de-regulated genes common in cell lines and primary tissue are primarily involved in ameboidal type cell migration and cell–cell junction organization. Additionally, we identify that ELF3-mutant cases in primary samples significantly overexpress PIK3C2B and ELF3 and PIK3C2B and ELF3 are significantly co-mutated in many cancer types. Our integrative analysis with existing Hi-C data further revealed the genes proximally located to ELF3, including PIK3C2B to be upregulated in ELF3 mutant cases, potentially as a result of truncated ELF3 protein product and subsequent changes in regulatory interactions.

Conclusions

Our results provide important insights about how ELF3 mutation contributes to bladder tumorigenesis and uncover previously unknown dependencies.

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Funding

This study is funded by EMBO Installation Grant No. 4148.

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Authors and Affiliations

  1. Izmir Biomedicine and Genome Center, 35340, Inciralti, Izmir, Turkey

    Perihan Yagmur Guneri-Sozeri & Serap Erkek-Ozhan

  2. Dokuz Eylül University Izmir International Biomedicine and Genome Institute, 35340, Inciralti, Izmir, Turkey

    Perihan Yagmur Guneri-Sozeri

  3. (Epi)Genomics of Cancer Group, Izmir Biomedicine and Genome Center, Dokuz Eylül University Health Campus, Mithatpaşa Caddesi No:58/5, 35330, Balçova, Izmir, Turkey

    Serap Erkek-Ozhan

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PYGS and SEO designed the study. PYGS analysed the data and performed the experiments. PYGS and SEO wrote the manuscript.

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11033_2022_7145_MOESM4_ESM.xlsx

Supplementary file4—Supplementary Table 1. Clinical Data of TCGA PanCancer Atlas for Bladder Urothelial Carcinoma. (XLSX 152 kb)

11033_2022_7145_MOESM5_ESM.xlsx

Supplementary file5—Supplementary Table 2. List of downregulated (A) and upregulated (B) genes in ELF3 mutant primary bladder cancer. List of downregulated (C) and upregulated (D) genes in ELF3 mutant bladder cancer cell lines. (XLSX 111 kb)

11033_2022_7145_MOESM6_ESM.xlsx

Supplementary file6—Supplementary Table 3. Genes associated with RT4-specific H3K27ac peaks and their linked GO Terms. (XLSX 9 kb)

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Guneri-Sozeri, P.Y., Erkek-Ozhan, S. Identification of the gene expression changes and gene regulatory aspects in ELF3 mutant bladder cancer. Mol Biol Rep 49, 3135–3147 (2022). https://doi.org/10.1007/s11033-022-07145-2

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