Medical Genomics, UCL Cancer Institute, University College London, London, WC1E 6DD UK.
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.
Genome Med. 2014 Dec 12;6(12):116. doi: 10.1186/s13073-014-0116-0. eCollection 2014.
The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics.
In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq.
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.
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.
肿瘤异种移植在癌症基因组学中是一种成熟的研究工具，但尚未在癌症表观基因组学中得到全面评估。
在这项研究中，我们使用 Infinium 450 K Beadchips 和 MeDIP-seq 评估了患者来源的肿瘤异种移植（PDXs）用于甲基组分析的适宜性。
控制混杂的宿主（小鼠）序列后，在罕见（骨肉瘤）和常见（结肠癌）癌症中比较原发性 PDXs 和匹配的患者肿瘤，结果表明，异种移植过程中，平均有 2.7%的检测到的 CpG 位点发生了主要（Δβ≥0.51）的癌症特异性甲基化变化。在原发性和继发性 PDX 之间进行第二轮异种移植后，未观察到明显的后续甲基化变化。基于使用公开可用的甲基化数据进行的计算模拟，我们还表明，未来比较两组 PDXs 的研究应在每组中使用 15 个或更多样本，以最大程度地减少异种移植相关甲基化变化对比较结果的影响。
我们在罕见和常见癌症中的结果表明，PDXs 是癌症表观基因组学的一种合适的发现工具，并且我们提供了如何克服观察到的局限性的指导。
