[Liquid biopsy for detection of H3K27m and BRAF V600E mutations in patients with diffuse brainstem tumors]

Despite the progress in understanding the pathogenesis of diffuse brainstem tumors, treatment of these neoplasms is usually empirical and conducted without morphological and molecular verification. Liquid biopsy is a minimally invasive technique providing data on tumor biology without standard biopsy. This method is based on analysis of cell-free nucleic acids (predominantly, extracellular DNA) in biological fluids with detection of specific mutations. Despite wide implementation in diagnosis and disease monitoring in extracranial malignancies, it is infrequently applied in neuro-oncology.

To estimate diagnostic value of liquid biopsy in detecting H3K27 and BRAF V600E mutations in patients with diffuse brainstem tumors.

Lumbar puncture with cerebrospinal fluid sampling was performed in 16 patients (5 children and 11 adults) with diffuse brainstem tumors verified by neuroimaging data. Cell-free DNA (cfDNA) was used in digital droplet PCR for determination of H3F3A K28M and BRAF V600E oncogenic missense variants. In 14 patients, investigation of cfDNA was performed in parallel with analysis of correspondent mutations in DNA derived from tumor tissue.

None patient had BRAF V600E mutation. H3F3A K28M variant was detected in 5 CSF samples and 6 tumor specimens from patients who underwent surgical biopsy. Thus, overall sensitivity of the method in determination of H3F3A K28M variant was 92.9% (13/14).

Liquid biopsy is highly informative for identifying the specific mutation H3F3A K28M and often verifies diffuse brainstem glioma without standard biopsy.