Figure 1.

Past, present, and future of H3K27M focused liquid biopsy. Seminal work identified disease-specific proteins in cerebrospinal fluid (CSF)—as well as patient serum and urine. The current state of the art is focused on serial quantification of H3K27M circulating tumor DNA in CSF and plasma using accurate droplet digital PCR assays and correlation with radiographic imaging to identify if liquid biopsy could be leveraged to predict response to treatment and help resolve pseudoprogression. Newer liquid biopsy approaches will leverage alternative and novel biomarkers such as mutant/modified histones derived from H3K27M mutant cells, routine, low-burden CSF collection via Ommaya reservoirs, as well as highly accurate and rapid sequencing approaches to simultaneously assay H3K27M along with other mutations (Created with BioRender.com).