| Literature DB >> 30349086 |
Sebastian Brabetz1,2,3, Sarah E S Leary4,5, Susanne N Gröbner1,2, Madison W Nakamoto5, Huriye Şeker-Cin2, Emily J Girard5, Bonnie Cole4, Andrew D Strand5, Karina L Bloom5, Volker Hovestadt6,7,8, Norman L Mack1,2,6, Fiona Pakiam5, Benjamin Schwalm1,2, Andrey Korshunov9,10, Gnana Prakash Balasubramanian1,2, Paul A Northcott2,11, Kyle D Pedro5, Joyoti Dey5,12, Stacey Hansen5, Sally Ditzler5, Peter Lichter6, Lukas Chavez1,2,13, David T W Jones1,2, Jan Koster14, Stefan M Pfister15,16,17, Marcel Kool18,19, James M Olson20,21.
Abstract
Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children's Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.Entities:
Mesh：
Year: 2018 PMID： 30349086 DOI： 10.1038/s41591-018-0207-3
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440