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Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone
Seon-Jin Yoon1,2, Junseong Park1, Dong-Su Jang3,4
1Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Abstract:
Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.
Insights
Investigating the cell-of-origin for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) reveals insights into cancer genesis. Understanding the subventricular zone
Area of Science:
- Neuro-oncology
- Cancer Biology
- Genetics
Background:
- Glioblastoma (GBM) remains a challenging brain disease with high recurrence and treatment resistance rates.
- Advances in single-cell resolution technologies are crucial for understanding GBM's cellular origins.
- The focus on IDH-wildtype GBM is critical due to its prevalence and aggressive nature.
Purpose of the Study:
- To review the cell-of-origin for IDH-wildtype glioblastoma.
- To explore the historical context and novel concepts of GBM genesis.
- To examine mutations linked to cellular senescence in the subventricular zone (SVZ).
Main Methods:
- Review of existing literature on GBM cellular origin.
- Analysis of mutations associated with senescence in SVZ cells.
- Biological validation using a mouse SVZ model for somatic mutations.
Main Results:
- The subventricular zone (SVZ) is implicated as a potential cell-of-origin for IDH-wildtype GBM.
- Specific mutations affecting cellular senescence in SVZ cells are identified.
- Experimental models confirm the biological relevance of these somatic mutations.
Conclusions:
- Understanding the cellular origins of IDH-wildtype GBM, particularly from the SVZ, is key to deciphering its genesis.
- Insights into GBM's cell-of-origin can inform the development of novel therapeutic strategies.
- This research may accelerate the discovery of new treatments for IDH-wildtype GBM.
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