Enduring epigenetic landmarks define the cancer microenvironment

Ruth Pidsley, Mitchell G. Lawrence, Elena Zotenko, Birunthi Niranjan, Aaron Statham, Jenny Song, Roman M. Chabanon, Wenjia Qu, Hong Wang, Michelle Richards, Shalima S. Nair, Nicola Armstrong, Hieu T. Nim, Melissa Papargiris, Preetika Balanathan, Hugh French, Timothy Peters, Sam Norden, Andrew Ryan, John PedersenJames G Kench, Roger J. Daly, Lisa Horvath, Phillip Stricker, Mark Frydenberg, Renea A. Taylor, Clare Stirzaker, Gail P. Risbridger, Susan J. Clark

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples.

Original languageEnglish
Pages (from-to)625-638
Number of pages14
JournalGenome Research
Volume28
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Cite this

Pidsley, R., Lawrence, M. G., Zotenko, E., Niranjan, B., Statham, A., Song, J., Chabanon, R. M., Qu, W., Wang, H., Richards, M., Nair, S. S., Armstrong, N., Nim, H. T., Papargiris, M., Balanathan, P., French, H., Peters, T., Norden, S., Ryan, A., ... Clark, S. J. (2018). Enduring epigenetic landmarks define the cancer microenvironment. Genome Research, 28(5), 625-638. https://doi.org/10.1101/gr.229070.117