Copy number signature analyses in prostate cancer reveal distinct etiologies and clinical outcomes

Abstract

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer, however, signatures of cancer genome copy number alteration (CNA) are still elusive in most cancer types, especially in prostate cancer (PC), which is particularly driven by complex genome alterations. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. Five copy number signatures are identified from human PC genome with this tool. The underlying driving forces for each signature have been illustrated. Sample clustering based on copy number signature exposure revealed considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. Copy number signature analyses provide distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.