DIPG-21. GENOMIC LANDSCAPE OF THE FIRST 100 TUMORS REGISTERED IN THE BIOLOGICAL MEDICINE FOR DIPG ERADICATION (BIOMEDE) TRIAL

BACKGROUND: Genomic analyses of DIPG have been so far mostly performed on autopsy samples or in retrospective studies. In the frame of the BIOMEDE randomized trial of three targeted therapies (erlotinib, everolimus, dasatinib) based on three biomarkers (EGFR, PTEN and PDGFRA respectively), a systematic whole exome and RNA sequencing of stereotactic biopsies was performed at diagnosis. These analyses were implemented to inform the results of the trial and define additional targets that could be used to guide therapies at relapse. PATIENTS AND METHODS: The results of the first 100 patients from France, Denmark and Belgium are presented. Seventy-five percent of the samples could be profiled for DNA &/or RNA, no frozen material was available for 6% of the tumors and only one sample was not contributive. RESULTS: Tumor samples from all but one patients included in the study on the basis of histology showed a loss of H3-K27 trimethylation. With respect to histone H3-K27M mutation, 75% of the samples were mutated in the H3F3A gene, 17% in the HIST1H3B gene and 8% were wild-type for all histone H3 genes. TP53 or PPM1D mutations were identified in 75% of H3F3A-K27M DIPG while never found in HIST1H3B-K27M tumours. ACVR1 mutations were almost exclusively found in HIST1H3B-K27M mutated samples, except for two histone H3 wild-type and one H3F3A-K27M mutated samples. Receptor Tyrosine-Kinases mutations or amplifications were restricted to H3F3A-K27M DIPG. Most tumors showed copy number variations. But gains of chromosome 1q and whole chromosome 2 were more frequent in the HIST1H3B-K27M mutated samples. On the opposite, chromothripsis-like structural copy number aberrations mostly affected TP53 or PPM1D mutated samples. Translocations were only rarely identified and none was recurrent. CONCLUSION: This study refines the description of the differences in the subtypes of DIPG and may support specific treatment adaptations with respect to potential biomarkers.