Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome

Abstract

Abstract:Currently, 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 cell cancer. To this end, DNA methylation profiles between vascularised tumour biopsy samples and devascularized nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort. We 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. Based on these results, we conclude that the impact of sampling procedures in clinical epigenetic studies should Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationbe considered, particularly after inducing hypoxia/ischemia, which occurs in many oncological surgery procedures through which tissues are harvested for translational research. conditions differed in the manner of sampling, we ran an additional study to analyse a possible sampling effect (biopsy vs. nephrectomy). Though this was not the case for VHLsubject of the previous paper -a clear sampling effect was observed for some loci and also appeared to be relevant in the actual treatment study. This implies that sampling procedure impacts results in cellular oncology studies. As the most likely underlying cause -hypoxiais relevant in many such studies, and the sampling study is unique in its kind (biopsy immediately followed by nephrectomy), we are confident that this paper is of general interest to researchers in the field of cellular oncology. independent clinical trial cohort. We found that six genes were differentially methylated in 45 the test samples, of which four were linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-46 1299, ANKRD2). Three of these genes were also found to be significantly differentially 47 methylated in the validation cohort, indicating that the observed effects are genuine. Based 48 on these results, we conclude that the impact of sampling procedures in clinical epigenetic 49 studies should be considered, particularly after inducing hypoxia/ischemia, which occurs in 50 many oncological surgery procedures through which tissues are harvested for translational 51 research. 52 53

DNA Methylation as Drug Sensitivity Marker in RCC: A Systematic Review

“…However, tissue sampling and clinical data registration are strenuous operations that require the strict implementation of legal precautions and standardized procedures in the sample acquisition, storage, and analysis. According to a study, sampling procedures and hypoxia/ischemia induce epigenetic modifications, in particular DNA demethylation, and their impact on RCC clinical epigenetic studies should be considered [ 50 ]. Another issue is the extent of tumor heterogeneity, which is expected to affect the results of epigenetic studies and the performance of potential biomarkers since subclones are likely responsible for progression and resistance to therapy [ 51 ].…”

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