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Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR

Author

Listed:
  • Christian M. Boßelmann

    (Cleveland Clinic
    Cleveland Clinic)

  • Costin Leu

    (Cleveland Clinic
    University College London
    The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston)

  • Tobias Brünger

    (The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston
    University of Cologne)

  • Lucas Hoffmann

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Sara Baldassari

    (Hôpital de la Pitié Salpêtrière)

  • Mathilde Chipaux

    (Rothschild Foundation Hospital)

  • Roland Coras

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Katja Kobow

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Hajo Hamer

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Daniel Delev

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Karl Rössler

    (Vienna General Hospital)

  • Christian G. Bien

    (Bielefeld University)

  • Thilo Kalbhenn

    (Bielefeld University
    Bielefeld University)

  • Tom Pieper

    (Vogtareuth)

  • Till Hartlieb

    (Vogtareuth
    Paracelsus Medical University)

  • Kerstin Becker

    (University of Cologne)

  • Lisa Ferguson

    (Cleveland Clinic)

  • Robyn M. Busch

    (Cleveland Clinic
    Cleveland Clinic)

  • Stéphanie Baulac

    (Hôpital de la Pitié Salpêtrière)

  • Peter Nürnberg

    (University of Cologne
    Faculty of Medicine and University Hospital Cologne)

  • Imad Najm

    (Cleveland Clinic)

  • Ingmar Blümcke

    (Cleveland Clinic
    Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Dennis Lal

    (Cleveland Clinic
    Cleveland Clinic
    The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston)

Abstract

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing. Here we confirm four known associations (BRAF, SLC35A2, MTOR, PTPN11), support eight associations without prior statistical support (FGFR1, PIK3CA, AKT3, NF1, PTEN, RHEB, KRAS, NRAS), and identify novel associations for two genes, DYRK1A and EGFR. Both novel genes show specific histopathological phenotypes, interact with LFE genes and pathways, and may represent promising candidates as biomarkers and potentially druggable targets.

Suggested Citation

  • Christian M. Boßelmann & Costin Leu & Tobias Brünger & Lucas Hoffmann & Sara Baldassari & Mathilde Chipaux & Roland Coras & Katja Kobow & Hajo Hamer & Daniel Delev & Karl Rössler & Christian G. Bien &, 2024. "Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54911-w
    DOI: 10.1038/s41467-024-54911-w
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    References listed on IDEAS

    as
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