Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant

Abstract

Background: Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity.

Purpose: To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile.

Material and methods: Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features.

Results: Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss (P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding.

Conclusion: Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.

Keywords: ATRX; Diffuse midline glioma H3 K27M-mutant; brain; magnetic resonance imaging.