Brain Tumors Originate in Normal Brain Tissue, New Research Reveals
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A groundbreaking study from the Korea Advanced Institute of Science and Technology (KAIST) has fundamentally altered our understanding of IDH-mutated gliomas, revealing these common brain tumors in young adults don’t simply appear – they develop slowly from cells within otherwise healthy brain tissue. This discovery opens new avenues for early diagnosis and therapies aimed at preventing recurrence.
MADRID, 9 Ene. (EUROPA PRESS) – For decades, treatment for IDH-mutated glioma, the most prevalent malignant brain tumor affecting adults under 50, has centered on removing visible tumor mass. However, this approach often falls short due to the cancer’s aggressive recurrence rate. Now, researchers have identified that the initial genetic mutation driving these tumors occurs in glial progenitor cells (GPCs) – cells capable of developing into various brain cells – long before a detectable tumor forms.
The research team’s findings, published this week, demonstrate that these mutated cells spread throughout the brain’s cortex, remaining largely undetected until additional genetic changes trigger rapid tumor growth. This challenges the long-held belief that brain tumors arise spontaneously at a specific location.
“This finding demonstrates for the first time that malignant brain tumors do not arise suddenly at a specific time, but rather begin within a normal brain and progress slowly over time,” explained a lead researcher involved in the study.
Unveiling the Origins with Spatial Transcriptomics
To pinpoint the origin of these tumors, the team meticulously analyzed both tumor tissue and surrounding normal brain cortex obtained during extensive surgical resections. Utilizing spatial transcriptomics – a cutting-edge technology that maps gene activity within tissues – they confirmed that the cells carrying the initial IDH mutation were, in fact, glial progenitor cells residing in the cerebral cortex.
Further validation came from an animal model, where introducing the same “driver mutation” found in patients into mouse GPCs successfully replicated the tumor development process. This provides compelling evidence for the role of these cells in the genesis of IDH-mutated gliomas.
Building on Previous Breakthroughs in Brain Tumor Research
This study builds upon a significant paradigm shift in brain tumor research initiated in 2018. That earlier work revealed that IDH wildtype glioblastoma, another aggressive brain cancer, originates not from the tumor itself, but from neural stem cells in the subventricular zone.
However, the current research clarifies a crucial distinction: while both IDH wildtype glioblastoma and IDH-mutated glioma are malignant brain cancers, their cellular origins and developmental pathways are fundamentally different. This underscores the need for tailored treatment strategies based on the specific subtype of brain tumor.
“Brain tumors may not start exactly where the tumor mass is visible,” stated Professor Seok-Gu Kang, co-corresponding author of the study. “A targeted approach to the cells of origin and the site of origin according to the brain tumor subtype will serve as a crucial key to changing the paradigm of early diagnosis and recurrence-suppressing treatment.”
New Therapies on the Horizon
The implications of this research are already driving innovation. Sovagen, a startup launched from KAIST, is developing an innovative RNA-based drug designed to suppress the progression and recurrence of IDH-mutated malignant brain tumors. Simultaneously, Severance Hospital is leveraging the findings to develop technologies for early detection and monitoring of mutant cells in refractory brain tumors, supported by the Korea-US Creating Breakthrough Results R&D project.
This research represents a pivotal moment in the fight against brain cancer, shifting the focus from treating established tumors to preventing their formation by targeting the vulnerable cells where they begin.
