Journal article
Enduring epigenetic landmarks define the cancer microenvironment
Genome Research, Vol.28(5), pp.625-638
2018
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.
Details
- Title
- Enduring epigenetic landmarks define the cancer microenvironment
- Authors/Creators
- R. Pidsley (Author/Creator) - Garvan Institute of Medical ResearchM.G. Lawrence (Author/Creator) - Monash UniversityE. Zotenko (Author/Creator) - Garvan Institute of Medical ResearchB. Niranjan (Author/Creator) - Monash UniversityA. Statham (Author/Creator) - Garvan Institute of Medical ResearchJ. Song (Author/Creator) - Garvan Institute of Medical ResearchR.M. Chabanon (Author/Creator) - Garvan Institute of Medical ResearchW. Qu (Author/Creator) - Garvan Institute of Medical ResearchH. Wang (Author/Creator) - Monash UniversityM. Richards (Author/Creator) - Monash UniversityS.S. Nair (Author/Creator) - Garvan Institute of Medical ResearchN.J. Armstrong (Author/Creator) - Garvan Institute of Medical ResearchH.T. Nim (Author/Creator) - Discovery InstituteM. Papargiris (Author/Creator) - Monash UniversityP. Balanathan (Author/Creator) - Monash UniversityH. French (Author/Creator) - Garvan Institute of Medical ResearchT. Petersen (Author/Creator)S. Norden (Author/Creator) - TissuPathA. Ryan (Author/Creator) - TissuPathJ. Pedersen (Author/Creator) - Discovery InstituteJ. Kench (Author/Creator) - Garvan Institute of Medical ResearchR.J. Daly (Author/Creator) - Monash UniversityL.G. Horvath (Author/Creator) - The University of SydneyP. Stricker (Author/Creator) - Garvan Institute of Medical ResearchM. Frydenberg (Author/Creator) - Monash UniversityR.A. Taylor (Author/Creator) - Peter MacCallum Cancer CentreC. Stirzaker (Author/Creator) - Garvan Institute of Medical ResearchG.P. Risbridger (Author/Creator) - Peter MacCallum Cancer CentreS.J. Clark (Author/Creator) - Garvan Institute of Medical Research
- Publication Details
- Genome Research, Vol.28(5), pp.625-638
- Publisher
- Cold Spring Harbor Laboratory Press.
- Identifiers
- 991005542857107891
- Copyright
- © 2018 Pidsley et al.
- Murdoch Affiliation
- School of Engineering and Information Technology
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.108 Molecular & Cell Biology - Cancer & Development
- 1.108.591 Cancer Stem Cells
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics