논문 (학술지)
Human glioblastoma arises from subventricular zone cells with low-level driver mutations
| 등록번호 | RPMS-2018-0190698188 | SCI 구분
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※구분 : SCI(SCIE포함), 비SCI |
SCI |
|---|---|---|---|
| 저자명 (주·공동저자) | Lee Joo Ho; Lee Jeong Eun; Kahng Jee Ye; Kim Se Hoon; Park Jun Sung; Yoon Seon Jin; Um Ji-Yong; Kim Woo Kyeong; Lee June-Koo; Park Junseong; Kim Eui Hyun; Lee Ji-Hyun; Lee Joon-Hyuk; Chung Won-Suk; Ju Young Seok; Park Sung-Hong; Chang Jong Hee; Kang Seok-Gu; Lee Jeong Ho | ||
| 논문구분 | 국외전문학술지 | 학술지명 | NATURE |
| ISSN | 0028-0836 | 학술지 출판일자 | 2018-08-01 |
| 학술지 볼륨번호 | 560 | 논문페이지 | 243 ~ 247 |
| 학술지 임팩트팩터 | 41.58 | 기여율 | 0 % |
| DOI | 10.1038/s41586-018-0389-3 | ||
| 초록 | Glioblastoma (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. | ||
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