Details

Autor(en) / Beteiligte

• Zhao, Shuang G.
• Chen, William S.
• Li, Haolong
• Foye, Adam
• Zhang, Meng
• Sjöström, Martin
• Aggarwal, Rahul
• Playdle, Denise
• Liao, Arnold
• Alumkal, Joshi J.
• Das, Rajdeep
• Chou, Jonathan
• Hua, Junjie T.
• Barnard, Travis J.
• Bailey, Adina M.
• Chow, Eric D.
• Perry, Marc D.
• Dang, Ha X.
• Yang, Rendong
• Moussavi-Baygi, Ruhollah
• Zhang, Li
• Alshalalfa, Mohammed
• Laura Chang, S.
• Houlahan, Kathleen E.
• Shiah, Yu-Jia
• Beer, Tomasz M.
• Thomas, George
• Chi, Kim N.
• Gleave, Martin
• Zoubeidi, Amina
• Reiter, Robert E.
• Rettig, Matthew B.
• Witte, Owen
• Yvonne Kim, M.
• Fong, Lawrence
• Spratt, Daniel E.
• Morgan, Todd M.
• Bose, Rohit
• Huang, Franklin W.
• Li, Hui
• Chesner, Lisa
• Shenoy, Tanushree
• Goodarzi, Hani
• Asangani, Irfan A.
• Sandhu, Shahneen
• Lang, Joshua M.
• Mahajan, Nupam P.
• Lara, Primo N.
• Evans, Christopher P.
• Febbo, Phillip
• Batzoglou, Serafim
• Knudsen, Karen E.
• He, Housheng H.
• Huang, Jiaoti
• Zwart, Wilbert
• Costello, Joseph F.
• Luo, Jianhua
• Tomlins, Scott A.
• Wyatt, Alexander W.
• Dehm, Scott M.
• Ashworth, Alan
• Gilbert, Luke A.
• Boutros, Paul C.
• Farh, Kyle
• Chinnaiyan, Arul M.
• Maher, Christopher A.
• Small, Eric J.
• Quigley, David A.
• Feng, Felix Y.

Titel

The DNA methylation landscape of advanced prostate cancer

Ist Teil von

• Nature genetics, 2020-08, Vol.52 (8), p.778-789

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 AR , MYC and ERG . Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer. Whole-genome bisulfite sequencing along with whole-genome and transcriptome sequencing of 100 prostate cancer metastases identifies genomic regions that are differentially methylated during disease progression and a novel epigenomic subtype.