The necessity for clinically accurate models of human cancer is clear, with the main concern being to recapitulate the corresponding human tumour as closely as possible with as little divergence in the behaviour of the model tumour from the actual tumour. Patient-derived xenografts (PDXs) – transplants of cancerous human tissue into immune-deficient mice – have been used widely since the 1980s for studying tumour biology and evaluating anticancer drugs. Although PDXs are not without their limitations and challenges, studies have shown that they do tend to retain the genomic and transcriptional features of the original tumour. But with a growing understanding of the importance of regulating gene expression in cancer development and progression, how useful are PDXs in studies of the epigenome? Stephan Beck from the University College London Cancer Institute, UK, and colleagues address this very question in a Genome Medicine study.
The authors focused on the epigenetic mechanism of DNA methylation, which is thought to have important implications for gene activation in cancers. They applied both array- and sequencing-based approaches on PDXs derived from rare and common cancers (osteosarcoma and bone cancer, and colon cancer, respectively), as well as using computational simulations. By comparing results from PDXs with corresponding patient tumours they found that, in both the rare and common cancer types, less than three percent of the methylome underwent major changes with xenografting. Furthermore, the authors suggest that the changes that did occur were likely due to tumour specificity rather than a generalised impact of the xenograft itself. Finally the authors provide guidance on how to minimise the impact of any confounding influences of PDXs on DNA methylation.
This is the first examination of how PDX models may affect DNA methylation patterns. By discovering that PDXs have little effect on the methylome, the authors provide convincing evidence that these xenografts are good models for epigenomic tumour studies and present a valuable discovery tool.
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