Analysis of 1386 Epileptogenic Brain Lesions Reveals Association with DYRK1A and EGFR

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 30

PMID 39616148

Authors

Christian M Bosselmann

Costin Leu

Tobias Brunger

Lucas Hoffmann

Sara Baldassari

Mathilde Chipaux

Roland Coras

Katja Kobow

Hajo Hamer

Daniel Delev

Karl Rossler

Christian G Bien

Thilo Kalbhenn

Tom Pieper

Till Hartlieb

Kerstin Becker

Lisa Ferguson

Robyn M Busch

Stephanie Baulac

Peter Nurnberg

Imad Najm

Ingmar Blumcke

Dennis Lal

Affiliations

Soon will be listed here.

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mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( 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

Citing Articles

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