TY - JOUR
T1 - Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR
AU - Bosselmann, Christian M.
AU - Leu, Costin
AU - Bruenger, Tobias
AU - Hoffmann, Lucas
AU - Baldassari, Sara
AU - Chipaux, Mathilde
AU - Coras, Roland
AU - Kobow, Katja
AU - Hamer, Hajo
AU - Delev, Daniel
AU - Roessler, Karl
AU - Bien, Christian G.
AU - Kalbhenn, Thilo
AU - Pieper, Tom
AU - Hartlieb, Till
AU - Becker, Kerstin
AU - Ferguson, Lisa
AU - Busch, Robyn M.
AU - Baulac, Stephanie
AU - Nuernberg, Peter
AU - Najm, Imad
AU - Bluemcke, Ingmar
AU - Lal, Dennis
N1 - Hartlieb: Center for Pediatric Neurology, Neurorehabilitation, and Epileptology, Schoen-Clinic, Vogtareuth, Rosenheim, Germany: Paracelsus Medical University, Salzburg, Austria
PY - 2024/11/30
Y1 - 2024/11/30
N2 - 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enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( 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.
AB - 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enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( 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.
KW - Growth-factor receptor
KW - Somatic mutations
KW - Reference panel
KW - Epilepsy
KW - Pathogenicity
KW - Frequencies
KW - System
KW - Cancer
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pmu_pure&SrcAuth=WosAPI&KeyUT=WOS:001367889200004&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1038/s41467-024-54911-w
DO - 10.1038/s41467-024-54911-w
M3 - Original Article
C2 - 39616148
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10429
ER -