Forschung & Innovation
Publikationen
Analysis of 1386 epileptogenic brain lesions reveals association with <i>DYRK1A</i> and <i>EGFR</i>
PMU Autor*in
Till Hartlieb
Alle Autor*innen
Christian M. Bosselmann, Costin Leu, Tobias Bruenger, Lucas Hoffmann, Sara Baldassari, Mathilde Chipaux, Roland Coras, Katja Kobow, Hajo Hamer, Daniel Delev, Karl Roessler, Christian G. Bien, Thilo Kalbhenn, Tom Pieper, Till Hartlieb, Kerstin Becker, Lisa Ferguson, Robyn M. Busch, Stephanie Baulac, Peter Nuernberg, Imad Najm, Ingmar Bluemcke, Dennis Lal
Fachzeitschrift
Nature Communications
Kurzfassung
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enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( 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.
Keywords
CANCER, SYSTEM, EPILEPSY, SOMATIC MUTATIONS, GROWTH-FACTOR RECEPTOR, Reference panel, Pathogenicity, Frequencies