**3. New advances: the future of genomics, epigenomics, and proteomics**

Taking into consideration that DIPG may represent a biologically distinct subclass of glioma, there is a great need for the comprehensive investigation of tumor biology. Therefore, studies in this rare type of cancer cannot be performed without the knowledge of genomics and proteomics. The development of new technologies that can rapidly analyze DNA, RNA, and proteins and the progress in bioinformatics area are substantial advances that have largely been achieved in the past years. Analysis of mRNA, methylation, and proteomic profiling of DIPGs compared to healthy brain tissue identified two distinct subgroups characterized by upregulation of N-Myc and Hedgehog signaling pathways [15]. Combinatory analysis of whole-genome and whole-exome sequencing, copy number alterations, methylation, and gene expression profiling revealed three molecular subgroups in DIPG, highlighting novel therapeutic targets [18]. The three molecular subgroups consisted of upregulation of N-Myc (histone 3 wild-type DIPGs), silent genomes with fewer copy number alterations, and histone 3 K27M mutant DIPGs with *ACVR1* and *TP53* mutations. DIPGs of silent and H3-K27M molecular subtypes would benefit from therapies targeting altered histone modifications, while patients of the N-Myc subtype would benefit from therapy targeting N-Myc or ID2. Furthermore, DIPGs of the N-Myc and silent subgroups lacked amplification of receptor tyrosine kinases, indicating the inefficacy of inhibitors targeting these kinase pathways [18]. Therefore, numerous combinatory analyses of DIPG have identified the importance of the synergistic genetic and epigenetic basis of this fatal childhood cancer.
