Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions. Academic Article uri icon

Overview

abstract

  • UNLABELLED: The most common somatic event in primary prostate cancer is a fusion between the androgen-related TMPRSS2 gene and the ERG oncogene. Tumors with these fusions, which occur early in carcinogenesis, have a distinctive etiology. A smaller subset of other tumors harbor fusions between TMPRSS2 and members of the ETS transcription factor family other than ERG. To assess the genomic similarity of tumors with non-ERG ETS fusions and those with fusions involving ERG, this study derived a transcriptomic signature of non-ERG ETS fusions and assessed this signature and ERG-related gene expression in 1,050 men with primary prostate cancer from three independent population-based and hospital-based studies. Although non-ERG ETS fusions involving ETV1, ETV4, ETV5, or FLI1 were individually rare, they jointly accounted for one in seven prostate tumors. Genes differentially regulated between non-ERG ETS tumors and tumors without ETS fusions showed similar differential expression when ERG tumors and tumors without ETS fusions were compared (differences explained: R2 = 69-77%), including ETS-related androgen receptor (AR) target genes. Differences appeared to result from similarities among ETS tumors rather than similarities among non-ETS tumors. Gene sets associated with ERG fusions were consistent with gene sets associated with non-ERG ETS fusions, including fatty acid and amino acid metabolism, an observation that was robust across cohorts. IMPLICATIONS: Considering ETS fusions jointly may be useful for etiologic studies on prostate cancer, given that the transcriptome is profoundly impacted by ERG and non-ERG ETS fusions in a largely similar fashion, most notably genes regulating metabolic pathways.

publication date

  • January 3, 2023

Research

keywords

  • Prostatic Neoplasms
  • Transcriptome

Identity

PubMed Central ID

  • PMC9812892

Scopus Document Identifier

  • 85145492053

Digital Object Identifier (DOI)

  • 10.1158/1541-7786.MCR-22-0446

PubMed ID

  • 36125519

Additional Document Info

volume

  • 21

issue

  • 1