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Genome Med. 2014 Dec 12;6(12):116. doi: 10.1186/s13073-014-0116-0. eCollection 2014.

Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics.

Author information

1
Medical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
2
Genetics and Cell Biology of Sarcoma, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Department of Biomedical Sciences, University of Westminster, London, W1W 6UW UK.
3
Medical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Translational Cancer Therapeutics Laboratory, CR-UK London Research Institute, London, WC2A 3LY UK.
4
Alacris Theranostics GmbH, 14195 Berlin, Germany.
5
Institute of Pathology, Medical University of Graz, 8036 Graz, Austria.
6
Department of Hematology and Medical Oncology, Charité Comprehensive Cancer Center, D-10117 Berlin, Germany.
7
EPO-Berlin-Buch GmbH, 13125 Berlin, Germany.
8
Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, CB10 1XL UK.
9
Genetics and Cell Biology of Sarcoma, UCL Cancer Institute, University College London, London, WC1E 6DD UK ; Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, London, HA7 4LP UK.

Abstract

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.

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