Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of > 1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
This work was supported by Cancer Research UK (grants C13468/A13982 and C13468/A23536), CRIS Cancer Foundation, Abbie’s Army and the DIPG Collaborative, the Cure Starts Now Foundation, Christopher’s Smile, McKenna Claire Foundation, Lyla Nsouli Foundation, National Institutes of Health (grants R01NS085336 and R01NS091620), The Dragon Master Foundation, The Kortney Rose Foundation, The Musella Foundation For Brain Tumor Research & Information, Gray Matters Foundation, Pediatric Brain Tumor Foundation, and the INSTINCT network funded by The Brain Tumour Charity, Great Ormond Street Children’s Charity, and Children with Cancer UK. The authors acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR. LTB was recipient of Sa˜ o Paulo Research Foundation fellowships (2011/08523-7 and 2012/08287-4). This study makes use of data generated by the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project, the Hospital for Sick Children, the McGill University-DKFZ Pediatric Brain Tumor Consortium, the International Cancer Genomics Consortium PedBrain Project and the Cancer Research UK Genomics Initiative (C13468/A14078) and supports the Children’s Brain Tumor Tissue Consortium and The Pacific Pediatric Neuro-Oncology Consortium (PNOC) CAVATICA: Project OPEN DIPG initiative.
info:eu-repo/semantics/publishedVersion