RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings

Cell Res. 2012 May;22(5):806-21. doi: 10.1038/cr.2012.30. Epub 2012 Feb 21.

Abstract

There are remarkable disparities among patients of different races with prostate cancer; however, the mechanism underlying this difference remains unclear. Here, we present a comprehensive landscape of the transcriptome profiles of 14 primary prostate cancers and their paired normal counterparts from the Chinese population using RNA-seq, revealing tremendous diversity across prostate cancer transcriptomes with respect to gene fusions, long noncoding RNAs (long ncRNA), alternative splicing and somatic mutations. Three of the 14 tumors (21.4%) harbored a TMPRSS2-ERG fusion, and the low prevalence of this fusion in Chinese patients was further confirmed in an additional tumor set (10/54=18.5%). Notably, two novel gene fusions, CTAGE5-KHDRBS3 (20/54=37%) and USP9Y-TTTY15 (19/54=35.2%), occurred frequently in our patient cohort. Further systematic transcriptional profiling identified numerous long ncRNAs that were differentially expressed in the tumors. An analysis of the correlation between expression of long ncRNA and genes suggested that long ncRNAs may have functions beyond transcriptional regulation. This study yielded new insights into the pathogenesis of prostate cancer in the Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Base Sequence
  • China
  • Chromosomes, Human, Pair 21
  • Cohort Studies
  • Gene Fusion*
  • Genome, Human
  • Humans
  • Male
  • Minor Histocompatibility Antigens
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Recurrence
  • Sequence Analysis, RNA*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Regulator ERG
  • Transcriptome
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism

Substances

  • Antigens, Neoplasm
  • ERG protein, human
  • KHDRBS3 protein, human
  • MIA2 protein, human
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins
  • RNA, Untranslated
  • RNA-Binding Proteins
  • Trans-Activators
  • Transcriptional Regulator ERG
  • USP9Y protein, human
  • PTEN Phosphohydrolase
  • Ubiquitin Thiolesterase
  • Serine Endopeptidases
  • TMPRSS2 protein, human