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Nat Med. 2018 Nov;24(11):1752-1761. doi: 10.1038/s41591-018-0207-3. Epub 2018 Oct 22.

A biobank of patient-derived pediatric brain tumor models.

Author information

1
Hopp Children's Cancer Center, NCT Heidelberg (KiTZ), Heidelberg, Germany.
2
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
4
Seattle Children's and University of Washington, Seattle, WA, USA.
5
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
6
Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
8
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
9
CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
10
Department of Neuropathology, Heidelberg University, Heidelberg, Germany.
11
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
12
Presage Biosciences, Seattle, WA, USA.
13
Department of Medicine, Division of Medical Genetics, University of California San Diego School of Medicine, La Jolla, CA, USA.
14
Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
15
Hopp Children's Cancer Center, NCT Heidelberg (KiTZ), Heidelberg, Germany. s.pfister@kitz-heidelberg.de.
16
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. s.pfister@kitz-heidelberg.de.
17
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany. s.pfister@kitz-heidelberg.de.
18
Hopp Children's Cancer Center, NCT Heidelberg (KiTZ), Heidelberg, Germany. m.kool@kitz-heidelberg.de.
19
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. m.kool@kitz-heidelberg.de.
20
Seattle Children's and University of Washington, Seattle, WA, USA. jolson@fredhutch.org.
21
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jolson@fredhutch.org.

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.

PMID:
30349086
DOI:
10.1038/s41591-018-0207-3
[Indexed for MEDLINE]

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