Journal article

Enduring epigenetic landmarks define the cancer microenvironment

Ruth Pidsley, Mitchell G Lawrence, Elena Zotenko, Birunthi Niranjan, Aaron Statham, Jenny Song, Roman M Chabanon, Wenjia Qu, Hong Wang, Michelle Richards, Shalima S Nair, Nicola J Armstrong, Hieu T Nim, Melissa Papargiris, Preetika Balanathan, Hugh French, Timothy Peters, Sam Norden, Andrew Ryan, John Pedersen Show all



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 a..

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Awarded by Cancer Australia

Awarded by National Health and Medical Research Council

Awarded by Cancer Institute of New South Wales Fellowship

Awarded by Prostate Cancer Foundation of Australia (Movember Young Investigator Grant)

Funding Acknowledgements

We thank the Epigenetics Research and Prostate Cancer Groups (Garvan Institute of Medical Research) and Prostate Cancer Research Group (Monash University and Peter MacCallum Cancer Centre) for helpful discussions; Dr. Brigid O'Gorman for help with figure preparation; Dr. Jeremy Grummet, Dr. Shomik Sengupta, and Dr. Ross Snow for patient recruitment; TissuPath Pathology for pathology support; the Australian Prostate Cancer BioResource for specimen collection; and the patients who donated their tissue. The results are based in part on data generated by the TCGA Research Network ( This work was funded by Cancer Australia (1044458), the National Health and Medical Research Council (Program 535903; Project grants 1070418 and 1106870; and Fellowships to S.J.C. [1063559], G.P.R. [1002648 and 1102752], M.G.L. [1035721], and R.J.D. [1058540]), Cancer Institute of New South Wales Fellowship to R.P. (14/ECF/1-23), Australian Prostate Cancer Research Centre-NSW, Prostate Cancer Foundation of Australia (Movember Young Investigator Grant to M.G.L. [YI0911]), Victorian Cancer Agency (Fellowships to R.A.T. and H.T.N.), RT Hall Trust, and TissuPath Pathology.