Journal article
The DNA methylation landscape of advanced prostate cancer
Shuang G Zhao, William S Chen, Haolong Li, Adam Foye, Meng Zhang, Martin Sjostrom, Rahul Aggarwal, Denise Playdle, Arnold Liao, Joshi J Alumkal, Rajdeep Das, Jonathan Chou, Junjie T Hua, Travis J Barnard, Adina M Bailey, Eric D Chow, Marc D Perry, Ha X Dang, Rendong Yang, Ruhollah Moussavi-Baygi Show all
NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2020
Abstract
Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes A..
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Awarded by Stand Up To Cancer-Prostate Cancer Foundation Prostate Cancer Dream Team Award
Awarded by National Institutes of Health (NIH)/National Cancer Institute (NCI)
Awarded by NIH/NCI
Awarded by Prostate Cancer Foundation (PCF)
Awarded by NIH
Awarded by Swedish Research Council (Vetenskapsradet)
Awarded by National Cancer Institute Early Detection Research Network
Funding Acknowledgements
We thank the patients who selflessly contributed samples to this study and without whom this research would not have been possible. We would also like to acknowledge the assistance of Steven Kronenberg and Barbara Panning. This research was supported by a Stand Up To Cancer-Prostate Cancer Foundation Prostate Cancer Dream Team Award (SU2C-AACR-DT0812 to E.J.S.) and by the Movember Foundation. Stand Up To Cancer is a division of the Entertainment Industry Foundation. This research grant was administered by the American Association for Cancer Research, the scientific partner of SU2C. S.G.Z., D.A.Q., Hui Li, R.A., J.T.H., R.B. and R.Y. were funded by Prostate Cancer Foundation Young Investigator Awards. F.Y.F. was funded by Prostate Cancer Foundation Challenge Awards. Additional funding was provided by a UCSF Benioff Initiative for Prostate Cancer Research award. F.Y.F. and A.A. were supported by National Institutes of Health (NIH)/National Cancer Institute (NCI) 1R01CA230516-01. F.Y.F. and N.M. were supported by NIH/NCI 1R01CA227025 and Prostate Cancer Foundation (PCF) 17CHAL06. F.Y.F. and A.M.C. were supported by NIH P50CA186786. A.M.C. is supported by NIH R35CA231996 and U01CA214170. D.A.Q. was funded by a BRCA Foundation Young Investigator Award. M.S. was supported by the Swedish Research Council (Vetenskapsradet) with grant number 2018-00382 and the Swedish Society of Medicine (Svenska Lakaresallskapet). L.A.G. was supported by K99/R00 CA204602 and DP2 CA239597, as well as the Goldberg-Benioff Endowed Professorship in Prostate Cancer Translational Biology. P.C.B. was supported by the NIH/NCI under award number P30CA016042 and by an operating grant from the National Cancer Institute Early Detection Research Network (1U01CA214194-01).