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Enduring epigenetic landmarks define the cancer microenvironment

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.

Type Journal
ISBN 1549-5469 (Electronic) 1088-9051 (Linking)
Authors 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.; Nim, H. T.; Papargiris, M.; Balanathan, P.; French, H.; Peters, 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.; Clark, S. J.
Responsible Garvan Author Prof Susan Clark
Publisher Name GENOME RESEARCH
Published Date 2018-05-01
Published Volume 28
Published Issue 5
Published Pages 625-638
Status Published in-print
DOI 10.1101/gr.229070.117
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/29650553