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Patient-derived Paediatric Brain Tumour Models

Resource to study key oncogenic drivers and evaluate novel treatment strategies
30 Oct 2018
Translational Research
Central Nervous System Malignancies

On 22 October 2018, a group of German, Dutch and US investigators reported in Nature Medicine that through the Children’s Oncology Group ACNS02B3 study, they have generated and comprehensively characterised 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of paediatric brain tumours. 

Brain tumours are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of paediatric brain tumours that may lead to novel therapeutic strategies. The authors wrote in the study background that better preclinical models that adequately reflect the biological heterogeneity are needed to evaluate new treatments. 

Patient-derived orthotopic xenograft models were found to be representative of the human tumours the researchers derived in this study 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 tumour subgroups and specific genetic alterations. 

These models and their molecular characterisation provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies. 

Patient-derived orthotopic xenograft models described in this study, as well as additional lines being developed and characterised, are catalogued online and shared with other researchers at the Brain Tumor Resource Laboratory. In addition, an online summary of each model and interactive access to the molecular and histopathological data can be found in the R2 PDX Explorer. Short-read sequencing data are available at the European Genome-phenome Archive, hosted by the European Bioinformatics Institute. Methylation and gene expression data have been deposited in the Gene Expression Omnibus

The DKFZ Genomics and Proteomics Core Facility, DKFZ Heidelberg, Germany, and the AMC Department of Oncogenomics, Amsterdam, The Netherlands performed high-throughput sequencing and microarray analyses. 

This work was supported by multiple US NIH grants, the Seattle Run of Hope, the Seattle Children’s Brain Tumor Research Endowment, the Dutch Cancer Foundations KWF, Deutsche Krebshilfe, and the Helmholtz International Graduate School for Cancer Research. 

Reference

Brabetz S, Leary SES, Gröbner SN, et al. A biobank of patient-derived pediatric brain tumor models. Nature Medicine; Published online 22 October 2018. DOI: 10.1038/s41591-018-0207-3.

Last update: 30 Oct 2018

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