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Enduring epigenetic landmarks define the cancer microenvironment

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.J.ORCID: 0000-0002-4477-293X, Nim, H.T., Papargiris, M., Balanathan, P., French, H., Petersen, T., Norden, S., Ryan, A., Pedersen, J., Kench, J., Daly, R.J., Horvath, L.G., Stricker, P., Frydenberg, M., Taylor, R.A., Stirzaker, C., Risbridger, G.P. and Clark, S.J. (2018) Enduring epigenetic landmarks define the cancer microenvironment. Genome Research, 28 (5). pp. 625-638.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): School of Engineering and Information Technology
Publisher: Cold Spring Harbor Laboratory Press.
Copyright: © 2018 Pidsley et al.
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