Aneuploidy drives lethal progression in prostate cancer

Significance Aneuploidy is usually quantified by measuring intracellular DNA content or chromosome structure and number. We show that the number of altered chromosome arms can be estimated from transcriptome profiling, which allows for assessing aneuploidy within repositories of archival, formalin-fixed, paraffin-embedded tumors. While aneuploidy impedes proliferation in primary cells, we show that it is a feature of aggressiveness in primary prostate cancers that are more likely to become lethal. Our data suggest that losses or gains of entire chromosome arms confers aggressiveness beyond affecting copy numbers of tumor suppressors or oncogenes on those arms. Beyond helping understand the etiology of aggressive prostate cancer, we propose that extent of aneuploidy could also be employed clinically to inform risk stratification and treatment.