Comprehensive genomic profiling of matched glioblastoma tumors, cell-lines and xenografts reveals genomic stability and adaptation to disparate growth environments

Glioblastoma Multiforme (GBM) is the most deadly brain tumor, and currently lacks effective treatment options. Brain tumor initiating cells (BTICs) and orthotopic xenografts are widely used in investigating GBM biology and new therapies for this aggressive disease. However, the genomic characteristics and molecular resemblance of these models to GBM tumors remain undetermined. We used massively parallel sequencing technology to decode the genomes and transcriptomes of BTICs and xenografts and their matched tumors in order to delineate the potential impacts of the distinct growth environments. Using data generated from whole‐genome sequencing of 201 samples and RNA sequencing of 118 samples, we showed that typical GBM genomic driver alterations found in the tumors were retained in BTICs and xenografts. In contrast, gene expression and methylation profiles indicated higher levels of divergence, likely due to the different growth environment for each sample type. These findings suggest that a comprehensive genomic understanding of in vitro and in vivo GBM model systems is crucial for interpreting data from drug‐screens, and can help control for biases introduced by cell culture conditions and the microenvironment in mouse models. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation from 31 matched parent tumor‐BTIC pairs and 4 matched trios of tumor-­BTIC-­‐xenograft.