Format

Send to

Choose Destination
Genome Res. 2018 May;28(5):625-638. doi: 10.1101/gr.229070.117. Epub 2018 Apr 12.

Enduring epigenetic landmarks define the cancer microenvironment.

Author information

1
Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
2
St. Vincent's Clinical School, UNSW Sydney, New South Wales 2052, Australia.
3
Prostate Research Group, Cancer Program-Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria 3800, Australia.
4
Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
5
Mathematics and Statistics, Murdoch University, Perth, Western Australia 6150, Australia.
6
Faculty of Information Technology, Monash University, Clayton, Victoria 3800, Australia.
7
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
8
Tissupath Pathology, Mount Waverley, Victoria 3149, Australia.
9
Cancer Research Division, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales 2010, Australia.
10
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales 2050, Australia.
11
Signalling Network Laboratory, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria 3800, Australia.
12
Chris O'Brien Lifehouse, Missenden Road, Camperdown, New South Wales 2050, Australia.
13
University of Sydney, Sydney, New South Wales 2050, Australia.
14
Department of Urology, St. Vincent's Prostate Cancer Centre, Sydney, New South Wales 2050, Australia.
15
Prostate Research Group, Cancer Program-Biomedicine Discovery Institute Department of Physiology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
16
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria 3010, Australia.
#
Contributed equally

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.

PMID:
29650553
PMCID:
PMC5932604
DOI:
10.1101/gr.229070.117
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center