Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

ABSTRACT: 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 repai

SUBMITTER: Quigley DA 

PROVIDER: S-EPMC6425931 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature