|Authors||Guilhamon, P., Butcher, L.M., Presneau, Nadège, Wilson, G.A., Feber, A., Paul, D.S., Schütte, M., Haybaeck, J., Keilholz, U., Hoffman, J., Ross, M.T., Flanagan, A.M. and Beck, S.|
Background: The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet
been comprehensively evaluated for cancer epigenomics.
Methods: In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis
using Infinium 450 K Beadchips and MeDIP-seq.
Results: Controlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient
tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites
undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure.
No significant subsequent methylation changes were observed after a second round of xenografting between primary
and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally
show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise
the impact of xenografting-associated changes in methylation on comparison results.
Conclusions: Our results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer
epigenomics and we provide guidance on how to overcome the observed limitations.