A domestic research team has, for the first time, confirmed that "IDH-mutant glioma," which tends to recur frequently and is difficult to treat, begins inside brain tissue that appears normal long before any visible tumor mass forms. There is hope that treatment strategies, which had focused on removing what is visible, could expand to find the starting point and catch it early.
A joint team led by Lee Jeong-ho, a professor at the KAIST Graduate School of Medical Science and Engineering, and Kang Seok-gu, a professor of neurosurgery at Yonsei University Severance Hospital, said on the 9th that they were the first in the world to identify that the cell of origin for IDH-mutant glioma is the "glial progenitor cell (GPC)" present in normal brain tissue. The findings were published in Science on the 9th.
IDH-mutant glioma is a malignant brain tumor that arises from mutations in a specific gene (IDH) and is known to be the most common malignant brain tumor among adults younger than 50. The problem is its high recurrence rate. Even after removing as much of the tumor mass as possible with surgery and combining radiation and chemotherapy, it often grows back over time.
The team conducted a detailed analysis not only of tumor tissue obtained through wide resection surgery, but also of the normal cerebral cortex surrounding the tumor. As a result, they confirmed that cells carrying IDH mutations exist even within tissue that appears normal under a microscope.
Put simply, it shows for the first time that a malignant brain tumor does not suddenly appear as a mass one day, but that mutated cells first arise within normal brain tissue and can progress slowly over a long period.
Going a step further, the team used spatial transcriptomics, a cutting-edge analysis method. This technology shows which genes are activated where, along with positional information within the tissue. In other words, it lays out the brain tissue like a map and allows a bird's-eye tracking of the states of cells.
Through this analysis, the team confirmed that the cell of origin carrying the IDH mutation is the glial progenitor cell present in the cerebral cortex. Glial progenitor cells exist in the normal brain and are precursor cells that can mature into glial cells. The researchers introduced key genetic alterations into glial progenitor cells in mice and recapitulated the process by which a brain tumor actually forms.
This achievement builds on the team's 2018 Nature paper. At that time, the researchers reported that glioblastoma, a representative malignant brain tumor, can start not in the main tumor mass but in neural stem cells of the subventricular zone. This time, by presenting that IDH-mutant glioma originates from glial progenitor cells in the cerebral cortex, they showed that brain tumors do not arise in a single way; depending on the type, the cell of origin and the starting location can fundamentally differ.
Kang said, "A brain tumor may not begin exactly where the tumor mass is visible," and added, "An approach that directly targets the cell and site of origin depending on the brain tumor subtype will be an important clue to changing the paradigm of early diagnosis and recurrence-suppressing treatment."
Based on the findings, KAIST faculty startup Sovargen Co., Ltd. is developing an RNA-based new drug to suppress the evolution and recurrence of IDH-mutant malignant brain tumors. Severance Hospital is also pursuing the development of technology to identify and control early mutated cells through a research and development (R&D) project as a research-driven hospital.
References
Science (2026), DOI: https://doi.org/10.1126/science.adt0559