Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome |
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| Authors: | Christophe Van Neste author-information" >,Alexander Laird,Fiach O’Mahony,Wim Van Criekinge,Dieter Deforce,Filip Van Nieuwerburgh,Thomas Powles,David J. Harrison,Grant D. Stewart,Tim De Meyer |
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| Affiliation: | 1.Laboratory of Pharmaceutical Biotechnology,Ghent University,Ghent,Belgium;2.Center for Medical Genetics,Ghent University,Ghent,Belgium;3.Edinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine,University of Edinburgh,Edinburgh,UK;4.Scottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC),Edinburgh,UK;5.MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine,University of Edinburgh,Edinburgh,UK;6.Biobix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modeling, Statistics and Bioninformatics,Ghent University,Ghent,Belgium;7.Renal Cancer Unit,The Royal Free Hospital,London,UK;8.Centre for Experimental Cancer Medicine, Bart’s Cancer Institute,Queen Mary University of London,London,UK;9.School of Medicine,University of St Andrews,Edinburgh,UK |
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| Abstract: | PurposeCurrently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer.MethodsDNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort.ResultsWe found that six genes were differentially methylated in the test samples, of which four were linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-1299, ANKRD2). Three of these genes were also found to be significantly differentially methylated in the validation cohort, indicating that the observed effects are genuine.ConclusionTissue ischaemia during normal surgical removal of tumour can cause epigenetic changes. Based on these results, we conclude that the impact of sampling procedures in clinical epigenetic studies should be considered and discussed, particularly after inducing hypoxia/ischaemia, which occurs in most oncological surgery procedures through which tissues are collected for translational research. |
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