Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes

PLoS Genet. 2021 May 4;17(5):e1009557. doi: 10.1371/journal.pgen.1009557. eCollection 2021 May.

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. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • DNA Copy Number Variations / genetics*
  • DNA Mutational Analysis*
  • Genome, Human / genetics
  • Genomic Instability
  • Genomics*
  • Humans
  • Male
  • Mutagenesis / genetics*
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / classification
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • Software*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor

Grants and funding

This work was supported by The National Natural Science Foundation of China (http://www.nsfc.gov.cn): 31771373 [X.-S.L.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.