RT Journal
A1 Pidsley, Ruth
A1 Lawrence, Mitchell G.
A1 Zotenko, Elena
A1 Niranjan, Birunthi
A1 Statham, Aaron
A1 Song, Jenny
A1 Chabanon, Roman M.
A1 Qu, Wenjia
A1 Wang, Hong
A1 Richards, Michelle
A1 Nair, Shalima S.
A1 Armstrong, Nicola J.
A1 Nim, Hieu T.
A1 Papargiris, Melissa
A1 Balanathan, Preetika
A1 French, Hugh
A1 Peters, Timothy
A1 Norden, Sam
A1 Ryan, Andrew
A1 Pedersen, John
A1 Kench, James
A1 Daly, Roger J.
A1 Horvath, Lisa G.
A1 Stricker, Phillip
A1 Frydenberg, Mark
A1 Taylor, Renea A.
A1 Stirzaker, Clare
A1 Risbridger, Gail P.
A1 Clark, Susan J.
T1 Enduring epigenetic landmarks define the cancer microenvironment
JF Genome Research 
JO Genome Research 
YR 2018 
FD May 01 
VO 28 
IS 5 
SP 625 
OP 638 
DO 10.1101/gr.229070.117 
UL http://genome.cshlp.org/content/28/5/625.abstract 
AB 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.