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Human glioblastoma arises from subventricular zone cells with low-level driver mutations.

DC Field Value Language
dc.contributor.author강석구-
dc.contributor.author김세훈-
dc.contributor.author김의현-
dc.contributor.author장종희-
dc.contributor.author윤선진-
dc.date.accessioned2018-09-28T08:57:09Z-
dc.date.available2018-09-28T08:57:09Z-
dc.date.issued2018-
dc.identifier.issn0028-0836-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/163262-
dc.description.abstractGlioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months1,2. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates3-5. However, there is a lack of direct genetic evidence from human patients with GBM4,6-10. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfNATURE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleHuman glioblastoma arises from subventricular zone cells with low-level driver mutations.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Neurosurgery-
dc.contributor.googleauthorJoo Ho Lee-
dc.contributor.googleauthorJeong Eun Lee-
dc.contributor.googleauthorJee Ye Kahng-
dc.contributor.googleauthorSe Hoon Kim-
dc.contributor.googleauthorJun Sung Park-
dc.contributor.googleauthorSeon Jin Yoon-
dc.contributor.googleauthorJi-Yong Um-
dc.contributor.googleauthorWoo Kyeong Kim-
dc.contributor.googleauthorJune-Koo Lee-
dc.contributor.googleauthorJunseong Park-
dc.contributor.googleauthorEui Hyun Kim-
dc.contributor.googleauthorJi-Hyun Lee-
dc.contributor.googleauthorJoon-Hyuk Lee-
dc.contributor.googleauthorWon-Suk Chung-
dc.contributor.googleauthorYoung Seok Ju-
dc.contributor.googleauthorSung-Hong Park-
dc.contributor.googleauthorJong Hee Chang-
dc.contributor.googleauthorSeok-Gu Kang-
dc.contributor.googleauthorJeong Ho Lee-
dc.identifier.doi10.1038/s41586-018-0389-3-
dc.contributor.localIdA05256-
dc.contributor.localIdA00036-
dc.contributor.localIdA00610-
dc.contributor.localIdA00837-
dc.contributor.localIdA03470-
dc.relation.journalcodeJ02289-
dc.identifier.eissn1476-4687-
dc.identifier.pmid30069053-
dc.identifier.urlhttp://dx.doi.org/10.1038/s41586-018-0389-3-
dc.contributor.alternativeNameKang, Seok Gu-
dc.contributor.alternativeNameKim, Se Hoon-
dc.contributor.alternativeNameKim, Eui Hyun-
dc.contributor.alternativeNameChang, Jong Hee-
dc.contributor.affiliatedAuthorYoon, Seon Jin-
dc.contributor.affiliatedAuthorKang, Seok Gu-
dc.contributor.affiliatedAuthorKim, Se Hoon-
dc.contributor.affiliatedAuthorKim, Eui Hyun-
dc.contributor.affiliatedAuthorChang, Jong Hee-
dc.citation.volume560-
dc.citation.startPage243-
dc.citation.endPage247-
dc.identifier.bibliographicCitationNATURE, Vol.560 : 243-247, 2018-
dc.identifier.rimsid58528-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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