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Liquid Biopsy Enables Early Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas

By LabMedica International staff writers
Posted on 28 Jan 2025

Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to debilitating symptoms such as intense pain, urinary incontinence, and tetraparesis, with limited treatment options available. More...

A new study has found that detecting H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could serve as a biomarker for identifying LMD in DMGs.

In the study, researchers from Niigata University’s Brain Research Institute (Niigata, Japan) collected 25 CSF samples from 22 DMG patients. The team utilized droplet digital PCR, a highly sensitive PCR technique, to detect trace amounts of ctDNA from the CSF of these patients. They successfully diagnosed LMD in DMGs by identifying H3K27M-mutant droplets in the ctDNA from the CSF samples. The findings, published in Pediatric Blood & Cancer, show that in two patients, LMD was diagnosed earlier than through traditional methods like MRI and CSF cytology. In one case, early diagnosis of LMD followed by aggressive interventions, including surgery, radiation, and intrathecal chemotherapy, resulted in long-term survival. The study demonstrates that detecting H3F3A K27M-mutant droplets in CSF ctDNA is not only diagnostic for LMD but also more sensitive than traditional diagnostic techniques, such as CSF cytology and MR imaging.

“We found that detecting circulating tumor DNA in the cerebrospinal fluid of diffuse midline glioma patients was more difficult than other brain tumor patients such primary central nervous system lymphoma and glioblastoma,” said Dr. Manabu Natsumeda, who led the research team. “However, when we were able to detect mutant tumor DNA, often the tumor had already spread to the cerebrospinal fluid, causing leptomeningeal disease. We think that early diagnosis and treatment of leptomeningeal disease in diffuse midline gliomas can improve survival.”

Related Links:
Niigata University Brain Research Institute


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