A biobank of patient-derived pediatric brain tumor models

Sebastian Brabetz, Sarah E.S. Leary, Susanne N. Gröbner, Madison W. Nakamoto, Huriye Şeker-Cin, Emily J. Girard, Bonnie Cole, Andrew D. Strand, Karina L. Bloom, Volker Hovestadt, Norman L. Mack, Fiona Pakiam, Benjamin Schwalm, Andrey Korshunov, Gnana Prakash Balasubramanian, Paul A. Northcott, Kyle D. Pedro, Joyoti Dey, Stacey Hansen, Sally DitzlerPeter Lichter, Lukas Chavez, David T.W. Jones, Jan Koster, Stefan M. Pfister, Marcel Kool, James M. Olson

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

106 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1752-1761
Aantal pagina's10
TijdschriftNature Medicine
Volume24
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 1 nov. 2018
Extern gepubliceerdJa

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