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- 조회753
Cancer Discov., Apr 16 2025, | https://doi.org/10.1158/2159-8290.CD-24-0234
Precancerous Cells Initiate Glioblastoma Evolution and Contribute to Intratumoral Heterogeneity
Hyun Jung Kim1,2, Keon Woo Kim1, Do Hyeon Cha1, Jihwan Yoo3, Eui Hyun Kim3, Jong Hee Chang3, Seok-Gu Kang3, Jung Won Park1, Ja Hye Kim1, Yeonhee Lee2, Eunha Lim2, Yiseul Kim2, Myeong Heui Kim4, Xue Li5,6, Joo Ho Lee5,6, Jeong Ho Lee1,4*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
2Department of Anatomy, Korea University College of Medicine, Seoul, South Korea
3Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
4Sovargen, Inc., Daejeon, South Korea
5Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
6Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
*Corresponding author: Jeong Ho Lee, M.D., Ph.D.
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
2Department of Anatomy, Korea University College of Medicine, Seoul, South Korea
3Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
4Sovargen, Inc., Daejeon, South Korea
5Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
6Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
*Corresponding author: Jeong Ho Lee, M.D., Ph.D.
Abstract
Neural stem cells (NSCs) in the subventricular zone (SVZ) are identified as cells-of-origin harboring driver mutations in glioblastoma (GBM), which is the most devastating brain tumor with highly heterogeneous nature. However, the sequential transformation of a limited number of mutation-harboring NSCs into a distant tumor with high intratumoral heterogeneity remains poorly understood. In this study, we have identified transcriptionally distinct types of mutation-harboring precancerous cells in our spontaneous, somatic mouse model recapitulating human GBM evolution as well as in tumor-free SVZ tissues from patients. These precancerous cells emerge via oligodendrocyte lineage specification, exhibiting unique transcriptional programs involving dysregulated translations and extracellular matrix remodeling. Subsequently, they give rise to heterogeneous tumor cell populations by activating multiple programs crucial for gliomagenesis. Our findings highlight the pivotal role of precancerous cells in tumor evolution and intratumoral heterogeneity, suggesting their potential as a novel therapeutic target for GBM.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-16)
- 국내 연구진
- 의약학 > 종양의학
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