A genomic and epigenomic atlas of prostate cancer in Asian populations

Nature. 2020 Apr;580(7801):93-99. doi: 10.1038/s41586-020-2135-x. Epub 2020 Mar 25.

Abstract

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

MeSH terms

  • Asian People / genetics*
  • Carrier Proteins / genetics
  • Cell Transformation, Neoplastic / genetics
  • China
  • Cohort Studies
  • DNA Helicases / genetics
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • Epigenesis, Genetic*
  • Epigenomics*
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Genomics*
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Humans
  • Male
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Prostatic Neoplasms / classification*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA-Seq
  • Transcriptome / genetics

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Nerve Tissue Proteins
  • ZNF292 protein, human
  • DNA Helicases
  • CHD1 protein, human