Abstract Details

Title Genomic Features of Histone Mutant Gliomas Based on Age: A Retrospective Cohort Study

Topic Neuro-oncology

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-006

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.

Authors/Disclosures
Jennifer H. Newman, MD (Jefferson Neurology) PRESENTER	Dr. Newman has nothing to disclose.
Elena Pentsova, MD (Memorial Sloan-Kettering Cancer Center)	The institution of Dr. Pentsova has received research support from YmAbs Therapeutics, Inc.
Neil Sielski, MD (NYU Langone Brain & Spine Tumor Center)	Dr. Sielski has nothing to disclose.
Subhiksha Nandakumar, MS	Miss Nandakumar has nothing to disclose.
Anne S. Reiner	Mrs. Reiner has nothing to disclose.
Matthias Karajannis	No disclosure on file
Ingo K. Mellinghoff, MD, FACP (Memorial Sloan Kettering Cancer Center)	Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Agios. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Black Diamond Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Voyager Therapeutics . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kazia Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Agios. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Black Diamond Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Debiopharm Group. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Puma Biotechnology. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Voyager Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DC Europa Ltd. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kazia Therapeutics. Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Dr. Mellinghoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cardinal Health. Dr. Mellinghoff has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier . Dr. Mellinghoff has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ASCO/JCO. The institution of Dr. Mellinghoff has received research support from Amgen. The institution of Dr. Mellinghoff has received research support from General Electric. The institution of Dr. Mellinghoff has received research support from Lilly. The institution of Dr. Mellinghoff has received research support from Kazia Therapeutics. An immediate family member of Dr. Mellinghoff has received research support from Vigeo Therapeutics. The institution of an immediate family member of Dr. Mellinghoff has received research support from Samus Therapeutics. The institution of Dr. Mellinghoff has received research support from Erasca .

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