作者
David A Quigley, Ha X Dang, Shuang G Zhao, Paul Lloyd, Rahul Aggarwal, Joshi J Alumkal, Adam Foye, Vishal Kothari, Marc D Perry, Adina M Bailey, Denise Playdle, Travis J Barnard, Li Zhang, Jin Zhang, Jack F Youngren, Marcin P Cieslik, Abhijit Parolia, Tomasz M Beer, George Thomas, Kim N Chi, Martin Gleave, Nathan A Lack, Amina Zoubeidi, Robert E Reiter, Matthew B Rettig, Owen Witte, Charles J Ryan, Lawrence Fong, Won Kim, Terence Friedlander, Jonathan Chou, Haolong Li, Rajdeep Das, Hui Li, Ruhollah Moussavi-Baygi, Hani Goodarzi, Luke A Gilbert, Primo N Lara, Christopher P Evans, Theodore C Goldstein, Joshua M Stuart, Scott A Tomlins, Daniel E Spratt, R Keira Cheetham, Donavan T Cheng, Kyle Farh, Julian S Gehring, Jörg Hakenberg, Arnold Liao, Philip G Febbo, John Shon, Brad Sickler, Serafim Batzoglou, Karen E Knudsen, Housheng H He, Jiaoti Huang, Alexander W Wyatt, Scott M Dehm, Alan Ashworth, Arul M Chinnaiyan, Christopher A Maher, Eric J Small, Felix Y Feng
发表日期
2018/7/26
期刊
Cell
卷号
174
期号
3
页码范围
758-769. e9
出版商
Elsevier
简介
While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications …
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DA Quigley, HX Dang, SG Zhao, P Lloyd, R Aggarwal… - Cell, 2018