Objective:

This study focuses on molecular characterization of DMG in all age groups. 

Background:

Diffuse midline glioma (DMG) is the second most common malignant pediatric brain tumor, occurring mainly in children 3–10 years old.  There is limited data on histone mutant gliomas concerning adult populations. 

Design/Methods:

This is a retrospective study of patients with histone mutated DMG who had tumor Integrated Mutation Profiling of Actionable Cancer Targets MSK-IMPACT testing.  We identified 66 patients comprising 32 women and 34 men, divided into three distinct age groups based upon adjusted WHO cohorts: 0-15 years (Pediatric, 34.3%), 15-39 years (Young Adult 41.8%), and over 39 years (Adult 22.4%). 

Results:

H3K27M mutations in our cohort consisted of H3F3A mutations (94%) followed by HIST1H3B (3%) and H3F3B (3%).  Among the pediatric age group, we discovered mutations such as TP53 in 61% of patients; PDGFRA in 35%, ATRX in 17%, KIT in 17%, RTK-RAS in 61%, PI3K in 39%, and NF1 in 4% of patients.  Within the young adult cohort, we found mutations in TP53 in 61% of patients; PDGFRA in 11%, ATRX in 29%, KIT in 4%, RTK-RAS in 64%, PI3K in 14%, and NF1 in 32% of patients. In adults, we noted TP53 mutations in 60% of patients, PDGFRA in 47%, ATRX in 0%, KIT in 33%, RTK-RAS in 93%, PI3K in 47%, and NF1 in 40% of patients. Median tumor mutation burden (TMB) values were as follows: Pediatric: 2.6, Young Adult: 3.5, and Adult: 4.1. 

Conclusions:

The mutation variations amongst age cohorts highlight the differences between tumor genetics among patients with DMG, which may have important implications for understanding age-related differences in tumor genetics and impact adjustments in treatment strategies.