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Origin of Glioblastoma Identified
[ Issue 164 Page 4 ] Tuesday, September 25, 2018, 17:06:03 Hyoyeon Kim Staff Reporter hyoyokim@kaist.ac.kr

The research team led by Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering has located the initial mutation that causes glioblastoma, one of the most aggressive and deadly brain tumors. The team has identified that glioblastoma originates from a mutation in the subventricular zone (SVZ) tissue away from the tumor mass. This finding is a reversal of the existing theory stating that the cause of glioblastoma is located in the tumor area and is expected to present a new direction for the development of a novel treatment for glioblastoma. The research was published in August on the Nature website under the title “Human glioblastoma arises from subventricular zone cells with low-level driver mutations”.

Due to the lack of understanding of the underlying cause of the disease, there is no perfect cure for glioblastoma. Most treatments involve a combination of surgery, chemotherapy, and radiotherapy, but the disease was deemed incurable until now. From the fact that glioblastoma tends to recur in a year after surgery, Professor Lee’s team judged that the cause of the disease lay in a brain area that is not the tumor area. The team thus focused on the SVZ, an area away from the tumor.

The team analyzed tumor tissue, normal cortical tissue, and SVZ tissue from 28 glioblastoma patients who received surgery between 2013 and 2017. Through deep sequencing of the triple-matched samples and single cell sequencing of patient brain tissue, they found that 56.3% of patients had low-level glioblastoma driver mutations in SVZ tissue that were observed at high levels in their corresponding tumors. Furthermore, using a genetically modified mouse model, they demonstrated that mutated cells in the SVZ leave the area and migrate to other parts of the brain, eventually developing into glioblastoma.

Professor Lee commented, “This research has its significance in that we have succeeded in identifying the cause of glioblastoma, which has the worst prognosis amongst cancer types, and went further to create an animal model for the disease. Since the animal model exactly replicates what we found in human patients, it will be possible to transfer viable therapeutics in this model for clinical use.” Based on the results of this research, the team will start developing a therapeutic drug to prevent cells in the SVZ from evolving into glioblastoma.

Professor Lee’s team had previously identified the principle and treatment method of intractable epilepsy for the first time. Based on this achievement, it is leading the worldwide development of diagnostic and therapeutic methods for intractable brain diseases together with global pharmaceutical companies. Professor Lee is the first Korean to participate as a key member in the World Congress of Epilepsy, which enacts international standards for genetic pathological diagnosis of intractable epilepsy.

Hyoyeon Kim Staff Reporter Archives  
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