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

Boßelmann CM, Leu C, Brünger T, Hoffmann L, Baldassari S, Chipaux M, Coras R, Kobow K, Hamer H, Delev D, Rössler K, Bien CG, Kalbhenn T, Pieper T, Hartlieb T, Becker K, Ferguson L, Busch RM, Baulac S, Nuernberg P, Najm I, Blümcke I, Lal D (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 15

Article Number: 10429

Issue: 1

DOI: 10.1038/s41467-024-54911-w

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enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( 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.

Authors with CRIS profile

Lucas Hoffmann Institute of Neuropathology Roland Coras Institute of Neuropathology Katja Kobow Institute of Neuropathology Hajo Hamer Professur für Epileptologie Daniel Delev Department of Neurosurgery Ingmar Blümcke Lehrstuhl für Neuropathologie

Additional Organisation(s)

Sonderforschungsbereich 1540/1 - Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems

Involved external institutions

Universität Bielefeld DE Germany (DE) Sorbonne Université FR France (FR) Cologne Center for Genomics DE Germany (DE) Cleveland Clinic US United States (USA) (US) Fondation Adolphe de Rothschild Hospital FR France (FR) Schön Kliniken DE Germany (DE) Universität zu Köln DE Germany (DE) Bethel Epilepsy Center DE Germany (DE) National Institute for Health Research GB United Kingdom (GB)

How to cite

APA:

Boßelmann, C.M., Leu, C., Brünger, T., Hoffmann, L., Baldassari, S., Chipaux, M.,... Lal, D. (2024). Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR. Nature Communications, 15. https://doi.org/10.1038/s41467-024-54911-w

MLA:

Boßelmann, Christian M., et al. "Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR." Nature Communications 15 (2024).

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