H3F3A mutations can be detected in bloodstream

Pediatric patients with diffuse midline gliomas have acquired a new tool: non-invasive liquid biopsy detecting essential variantions of H3F3A gene.

Histone genes (HIST1H3B/C, HIST2H3C, H3F3A) mutations are associated with lower survival of brain cancer patients. Among them, a mutation called K27M in H3F3A gene gained recognition on a global level – World Health Organization separated a new class of gliomas: diffuse midline glioma with H3 K27-mutant.

Detection of eventual mutations in the gene could considerably support diagnosis and therapy. However, the procedure to date required invasive brain biopsy and cerebrospinal fluid collection.

In the experiments on samples of 48 patients, the researchers have tested a non-invasive approach utilizing blood samples. Digital droplet PCR (ddPCR) device, through sequences specific for the gene, amplified (serially duplicate molecules) and detected rare mutations with false positive rate equaling or even below 0.001%.

The test was expanded to clinical trial PNOC003, where it successfully identified mutations and predicted the outcome of therapy.

More: “Clinically Relevant and Minimally Invasive Tumor Surveillance of Pediatric Diffuse Midline Gliomas Using Patient-Derived Liquid Biopsy”, E. Panditharatna et al., 2018, doi:10.1158/1078-0432.ccr-18-1345.