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Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer

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  • Nikolaos M. R. Lykoskoufis

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics
    NGS-AI JSR Life Sciences, Route de la Corniche 3)

  • Evarist Planet

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Halit Ongen

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics)

  • Didier Trono

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Emmanouil T. Dermitzakis

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics)

Abstract

Transposable elements (TEs) are prevalent repeats in the human genome, play a significant role in the regulome, and their disruption can contribute to tumorigenesis. However, TE influence on gene expression in cancer remains unclear. Here, we analyze 275 normal colon and 276 colorectal cancer samples from the SYSCOL cohort, discovering 10,231 and 5,199 TE-expression quantitative trait loci (eQTLs) in normal and tumor tissues, respectively, of which 376 are colorectal cancer specific eQTLs, likely due to methylation changes. Tumor-specific TE-eQTLs show greater enrichment of transcription factors, compared to shared TE-eQTLs suggesting specific regulation of their expression in tumor. Bayesian networks reveal 1,766 TEs as mediators of genetic effects, altering the expression of 1,558 genes, including 55 known cancer driver genes and show that tumor-specific TE-eQTLs trigger the driver capability of TEs. These insights expand our knowledge of cancer drivers, deepening our understanding of tumorigenesis and presenting potential avenues for therapeutic interventions.

Suggested Citation

  • Nikolaos M. R. Lykoskoufis & Evarist Planet & Halit Ongen & Didier Trono & Emmanouil T. Dermitzakis, 2024. "Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-42405-0
    DOI: 10.1038/s41467-023-42405-0
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    References listed on IDEAS

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    1. Olivier Delaneau & Halit Ongen & Andrew A. Brown & Alexandre Fort & Nikolaos I. Panousis & Emmanouil T. Dermitzakis, 2017. "A complete tool set for molecular QTL discovery and analysis," Nature Communications, Nature, vol. 8(1), pages 1-7, August.
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    3. Michaël Imbeault & Pierre-Yves Helleboid & Didier Trono, 2017. "KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks," Nature, Nature, vol. 543(7646), pages 550-554, March.
    4. Scutari, Marco, 2010. "Learning Bayesian Networks with the bnlearn R Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 35(i03).
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