Research says brain cancer starts many years before detection

By Sola Ogundipe

Scientists have found that a common brain cancer may begin in normal-looking brain cells years before a tumour appears. The discovery points to new ways to detect and treat the disease earlier, potentially reducing recurrence.

The scientists in South Korea discovered that normal-looking brain cells can acquire the first IDH mutation and quietly spread through the brain’s cortex long before a tumour mass forms. This early, hidden phase may explain why the cancer is so difficult to eliminate and points to new possibilities for earlier detection and preventing recurrence.

  IDH-mutant gliomas are those nasty tumours that usually hit people under 50, now scientists have found that the tumour isn’t the beginning, rather, it’s the finish line.

 A team led by Professors Jeong Ho Lee and Seok-Gu Kang found that these cancers start in normal brain cells, specifically Glial Progenitor Cells (GPCs), years before a doctor can see a thing.

These cells look healthy under a microscope, but they’ve already picked up a quiet mutation and started wandering through the brain’s cortex. By the time a mass actually forms, the seeds have been sown all over the place.

 The researchers didn’t just stumble onto this, they used spatial transcriptomics which is basically a high-tech “who is doing what and where” map, to track these mutated cells in tissue that looked totally fine to the naked eye.

  The findings published in the journal Science draws a line between different types of brain cancer. Back in 2018, this same group found that glioblastomas start in neural stem cells. But these gliomas have their own origin story in the cortex.

A joint research team by KAIST led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering and Professor Seok-Gu Kang of Yonsei University Severance Hospital identified the cellular origin of IDH-mutant glioma. The team found that these tumors arise from Glial Progenitor Cells (GPCs) that exist in normal brain tissue.

To reach this conclusion, the researchers closely examined tumour samples collected during extensive surgical removal, along with nearby brain tissue that appeared healthy. They found that cells carrying the IDH mutation were already present in brain regions that looked completely normal to the naked eye.

These findings provide the first clear evidence that malignant brain tumors do not suddenly appear at a single moment. Instead, they can begin quietly within normal brain tissue and evolve gradually over many years before forming a detectable mass.

To confirm the identity of these early mutated cells, the team used “spatial transcriptomics” — a cutting-edge analysis technology that shows “which genes are operating where” simultaneously. This approach confirmed that the mutation-bearing cells were Glial Progenitor Cells (GPCs) located in the cerebral cortex.

The researchers also recreated the process in animals. By introducing the same genetic “driver mutation” found in patients into the GPCs of mice, they successfully reproduced key steps of brain tumour development.

This study builds on earlier work by the same research group. In 2018, they reported that IDH wildtype glioblastoma, another aggressive brain cancer, originates from neural stem cells in the subventricular zone — the source of new brain cells in the adult brain (Lee et al., Nature, 2018).

The new findings show that although IDH wildtype glioblastoma and IDH-mutant glioma are both malignant brain tumors, they arise from different types of cells and begin in different regions of the brain. This confirms that brain cancers can follow distinct biological paths depending on their subtype.

Professor Seok-Gu Kang explained the importance of this shift: “Brain tumours may not start exactly where the tumour mass is visible. A target approach focused on the origin cells and the site of origin according to the brain tumour subtype will serve as a crucial clue to changing the paradigm of early diagnosis and recurrence suppression treatment.”

 Dr. Jung Won Park (Postdoctoral Researcher at KAIST Graduate School of Medical Science and Engineering), a neurosurgeon and the study’s sole first author, emphasized the collaboration behind the work.

 ”This achievement was made possible by combining KAIST’s world-class basic science research capabilities with the clinical expertise of Yonsei Severance Hospital. The question I kept asking while treating patients — ‘Where does this tumor originate?’ — was the starting point of this research.”

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