Cited 81 times in
BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors
DC Field | Value | Language |
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dc.contributor.author | 강훈철 | - |
dc.contributor.author | 김동석 | - |
dc.contributor.author | 김세훈 | - |
dc.date.accessioned | 2019-04-03T07:47:49Z | - |
dc.date.available | 2019-04-03T07:47:49Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/167748 | - |
dc.description.abstract | Pediatric brain tumors are highly associated with epileptic seizures1. However, their epileptogenic mechanisms remain unclear. Here, we show that the oncogenic BRAF somatic mutation p.Val600Glu (V600E) in developing neurons underlies intrinsic epileptogenicity in ganglioglioma, one of the leading causes of intractable epilepsy2. To do so, we developed a mouse model harboring the BRAFV600E somatic mutation during early brain development to reflect the most frequent mutation, as well as the origin and timing thereof. Therein, the BRAFV600E mutation arising in progenitor cells during brain development led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to high proliferation of glial lineage cells. RNA sequencing analysis of patient brain tissues with the mutation revealed that BRAFV600E-induced epileptogenesis is mediated by RE1-silencing transcription factor (REST), which is a regulator of ion channels and neurotransmitter receptors associated with epilepsy. Moreover, we found that seizures in mice were significantly alleviated by an FDA-approved BRAFV600E inhibitor, vemurafenib, as well as various genetic inhibitions of Rest. Accordingly, this study provides direct evidence of a BRAF somatic mutation contributing to the intrinsic epileptogenicity in pediatric brain tumors and suggests that BRAF and REST could be treatment targets for intractable epilepsy. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Nature Publishing Company | - |
dc.relation.isPartOf | NATURE MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pediatrics (소아청소년과학교실) | - |
dc.contributor.googleauthor | Hyun Yong Koh | - |
dc.contributor.googleauthor | Se Hoon Kim | - |
dc.contributor.googleauthor | Jaeson Jang | - |
dc.contributor.googleauthor | Hyungguk Kim | - |
dc.contributor.googleauthor | Sungwook Han | - |
dc.contributor.googleauthor | Jae Seok Lim | - |
dc.contributor.googleauthor | Geurim Son | - |
dc.contributor.googleauthor | Junjeong Choi | - |
dc.contributor.googleauthor | Byung Ouk Park | - |
dc.contributor.googleauthor | Won Do Heo | - |
dc.contributor.googleauthor | Jinju Han | - |
dc.contributor.googleauthor | Hyunjoo Jenny Lee | - |
dc.contributor.googleauthor | Daeyoup Lee | - |
dc.contributor.googleauthor | Hoon-Chul Kang | - |
dc.contributor.googleauthor | Minho Shong | - |
dc.contributor.googleauthor | Se-Bum Paik | - |
dc.contributor.googleauthor | Dong Seok Kim | - |
dc.contributor.googleauthor | Jeong Ho Lee | - |
dc.identifier.doi | 10.1038/s41591-018-0172-x | - |
dc.contributor.localId | A00102 | - |
dc.contributor.localId | A00402 | - |
dc.contributor.localId | A00610 | - |
dc.relation.journalcode | J02296 | - |
dc.identifier.eissn | 1546-170X | - |
dc.identifier.pmid | 30224756 | - |
dc.identifier.url | https://www.nature.com/articles/s41591-018-0172-x | - |
dc.contributor.alternativeName | Kang, Hoon Chul | - |
dc.contributor.affiliatedAuthor | 강훈철 | - |
dc.contributor.affiliatedAuthor | 김동석 | - |
dc.contributor.affiliatedAuthor | 김세훈 | - |
dc.citation.volume | 24 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1662 | - |
dc.citation.endPage | 1668 | - |
dc.identifier.bibliographicCitation | NATURE MEDICINE, Vol.24(11) : 1662-1668, 2018 | - |
dc.identifier.rimsid | 58345 | - |
dc.type.rims | ART | - |
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