2. Academic Validation
  3. A biobank of patient-derived pediatric brain tumor models

A biobank of patient-derived pediatric brain tumor models

  • Nat Med. 2018 Nov;24(11):1752-1761. doi: 10.1038/s41591-018-0207-3.
Sebastian Brabetz 1 2 3,  Sarah E S Leary 4 5,  Susanne N Gröbner 1 2,  Madison W Nakamoto 5,  Huriye Şeker-Cin 2,  Emily J Girard 5,  Bonnie Cole 4,  Andrew D Strand 5,  Karina L Bloom 5,  Volker Hovestadt 6 7 8,  Norman L Mack 1 2 6,  Fiona Pakiam 5,  Benjamin Schwalm 1 2,  Andrey Korshunov 9 10,  Gnana Prakash Balasubramanian 1 2,  Paul A Northcott 2 11,  Kyle D Pedro 5,  Joyoti Dey 5 12,  Stacey Hansen 5,  Sally Ditzler 5,  Peter Lichter 6,  Lukas Chavez 1 2 13,  David T W Jones 1 2,  Jan Koster 14,  Stefan M Pfister 15 16 17,  Marcel Kool 18 19,  James M Olson 20 21
Affiliations

Affiliations

  • 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. [email protected].
  • 16 Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [email protected].
  • 17 Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany. [email protected].
  • 18 Hopp Children's Cancer Center, NCT Heidelberg (KiTZ), Heidelberg, Germany. [email protected].
  • 19 Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [email protected].
  • 20 Seattle Children's and University of Washington, Seattle, WA, USA. [email protected].
  • 21 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [email protected].
PMID: 30349086 DOI: 10.1038/s41591-018-0207-3
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.

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