Changes in the concentration of freely circulating mutant DNA and wild-type DNA of the H3F3А (K27M) gene in the blood and cerebrospinal fluid of children with diffuse midline gliomas during a course of radiation therapy

Abstract

Purpose of the study. To study the possibility of detecting freely circulating DNA of the H3F3A (K27M) gene in blood plasma and cerebrospinal fluid in the lumbar spine in children with diffuse midline gliomas (DMG) during a course of radiation therapy (RT).Materials and methods. Molecular genetic studies were carried out by digital PCR. 96 samples of lumbar cerebrospinal fluid and 288 samples of peripheral blood plasma from 96 pediatric patients were analyzed. The concentration of circulating tumor (ctDNA) mutant DNA and wild-type DNA of the H3F3A (K27M) gene was determined in the studied material against the background of a course of RT. Lumbar cerebrospinal fluid sampling was performed once at the beginning of therapy, blood sampling was performed three times: The 1st test before the start of RT, the 2nd against the background of a total dose 10–15 Gy, and the 3rd after the completion of the RT course. Patients are divided into the following groups: patients with stabilization of brain tumor growth during early magnetic resonance (MR) control 3 months after completion of the course of RT; patients with disease progression during the same follow-up period who underwent radiation or chemoradiotherapy.Results. When the disease stabilized after a RT course during treatment, the concentration level of both the mutant variant of ctDNA and wild-type ctDNA significantly decreased in the third blood fraction. The absence of changes or an increase in the concentration of mutant ctDNA and wild-type ctDNA of the H3F3A (K27M) gene by the end of the course of radiation therapy was typical for patients with disease progression in the form of the appearance of metastatic foci in the central nervous system or continued tumor growth. At the same time, the concentration of wild-type DNA of the H3F3A (K27M) gene in the group of patients with progression was higher both in the lumbar cerebrospinal fluid and in the first fraction of blood plasma.Connclusion. Determination of the concentration and dynamics of circulating tumor DNA of the mutant and wild-type of the H3F3A (K27M) gene in blood plasma and lumbar cerebrospinal fluid in children with diffuse median gliomas of the brain during radiation therapy is promising from the point of view of predicting the effectiveness of therapy.

Keywords

• glioma
• diffuse median glioma
• digital drip pcr
• h3f3a
• k27m
• circulating tumor dna (ctdna)