TY  - JOUR
AU  - Brabetz, Sebastian
AU  - Leary, Sarah E S
AU  - Gröbner, Susanne
AU  - Nakamoto, Madison W
AU  - Şeker-Cin, Huriye
AU  - Girard, Emily J
AU  - Cole, Bonnie
AU  - Strand, Andrew D
AU  - Bloom, Karina L
AU  - Hovestadt, Volker
AU  - Mack, Norman
AU  - Pakiam, Fiona
AU  - Schwalm, Benjamin
AU  - Korshunov, Andrey
AU  - Balasubramanian, Gnana Prakash
AU  - Northcott, Paul A
AU  - Pedro, Kyle D
AU  - Dey, Joyoti
AU  - Hansen, Stacey
AU  - Ditzler, Sally
AU  - Lichter, Peter
AU  - Chavez, Lukas
AU  - Jones, David
AU  - Koster, Jan
AU  - Pfister, Stefan
AU  - Kool, Marcel
AU  - Olson, James M
TI  - A biobank of patient-derived pediatric brain tumor models.
JO  - Nature medicine
VL  - 24
IS  - 11
SN  - 1546-170X
CY  - New York, NY
PB  - Nature America Inc.
M1  - DKFZ-2018-01936
SP  - 1752 - 1761
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30349086
DO  - DOI:10.1038/s41591-018-0207-3
UR  - https://inrepo02.dkfz.de/record/141665
ER  -