Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticle


Christophe Van Neste, Alexander Laird, Fiach O'Mahony, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerbugh, Thomas Powles, David James Harrison, Grant D. Stewart, Tim De Meyer

School/Research organisations


Background: Sample collection for clinical epigenetics research often occurs at the time of surgical excision of a diseased organ. However, this approach may compromise the epigenetic profile under study. The use of different sampling procedures during a study can often not be avoided, but may in theory lead to biased results.
The effect of tissue sampling approach on DNA methylation is studied here using clear cell renal cell cancer (ccRCC) as a model. A comparison of the DNA methylation profiles between vascularised tumour biopsy samples and subsequent devascularised nephrectomy samples obtained from the same two individuals (total of 6 samples per individual) was undertaken. Validation of the results was performed using biopsy and nephrectomy samples obtained from 14 patients included in a ccRCC clinical trial (SuMR; identifier: NCT01024205).
Findings: Using MBD2 sequencing, the methylome was analysed for all samples and differential methylome regions were retrieved. The results, from the test set, show six differentially methylated genes, of which four were clearly linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-1299, and ANKRD2). To validate these findings, it was evaluated whether these loci were also featured by differential methylation in the clinical trial cohort with a similar experimental design to the test set. Three of the six genes are again significantly differentially methylated, showing an overall clear impact of renal artery clamping on DNA methylation.
Conclusions: Renal artery ligation modulates the ccRCC methylome, impacting methylation of ischaemia and hypoxia associated genes. Results from devascularised surgical resection specimens do not accurately reflect findings from tumour biopsies.


Original languageEnglish
Pages (from-to)293-297
Number of pages5
JournalCellular Oncology
Issue number3
Early online date10 Jan 2017
Publication statusPublished - Jun 2017

    Research areas

  • Hypoxia, Epigenetics, Methylation, Biobanking

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031

    Sarr, A., Bré, J., Um, I. H., Chan, T. H., Mullen, P., Harrison, D. J. & Reynolds, P. A., 21 May 2019, In : Scientific Reports. 9, 13 p., 7643.

    Research output: Contribution to journalArticle

  2. Raman spectroscopy investigation of biochemical changes in tumor spheroids with aging and after treatment with staurosporine

    Jamieson, L. E., Harrison, D. J. & Campbell, C. J., May 2019, In : Journal of Biophotonics. 12, 5, e201800201.

    Research output: Contribution to journalArticle

  3. Automated tumour budding quantification by machine learning augments TNM staging in muscle-invasive bladder cancer prognosis

    Brieu, N., Gavriel, C., Nearchou, I. P., Harrison, D. J., Schmidt, G. & Caie, P. D., 26 Mar 2019, In : Scientific Reports. 9, 5174.

    Research output: Contribution to journalArticle

  4. Colorectal cancer outcome prediction from H&E whole slide images using machine learning and automatically inferred phenotype profiles

    Yue, X., Dimitriou, N., Caie, P., Harrison, D. & Arandjelovic, O., 18 Mar 2019, Proceedings of 11th International Conference on Bioinformatics and Computational Biology, BICOB 2019: Honolulu; United States; 18 March 2019 through 20 March 2019. Eulenstein, O., Al-Mubaid, H. & Ding, Q. (eds.). EasyChair, p. 139-127 11 p. (EPiC Series in Computing; vol. 60).

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

ID: 248518466