ERG

Overview

ERG (ETS-Related Gene) is a transcription factor of the ETS family. In prostate cancer, ERG is the most common fusion partner with TMPRSS2 (TMPRSS2-ERG), occurring in ~50% of cases and representing one of the most frequent structural rearrangements in human cancer. ERG fusion overexpression drives AR-dependent transcriptional programs and is a defining molecular event in a large subset of prostate cancers.

Alterations observed in the corpus

  • TMPRSS2-ERG fusion observed in 13 of 44 prostate cancer PDX models (MDA PCa PDX series); ERG overexpression is dependent on TMPRSS2 fusion and occurs in AR-expressing (adenocarcinoma) models PMID:38488813.
  • TMPRSS2-ERG fusions depleted in MSI-H/dMMR prostate cancer (3%) compared with TMB-H/MSS (12%) and TMB-L/MSS tumors (p=0.015), suggesting that the ERG fusion pathway and mismatch repair deficiency represent distinct oncogenic routes PMID:38949888.
  • ERG was identified as a recurrently rearranged gene in prostate cancer through integrative genomic profiling of the MSKCC cohort PMID:20579941
  • TMPRSS2-ERG ETS rearrangements present in up to 50% of prostate cancers; mutually exclusive with SPOP mutations in a 112-tumor WES cohort (Broad) PMID:22610119
  • TMPRSS2-ERG fusion identified as the most prevalent ETS gene rearrangement in prostate cancer WES cohort (Michigan, 112 tumors); ERG fusions detected in approximately 50% of cases PMID:22722839
  • TMPRSS2-ERG fusion arises via 21q intronic deletion within chromoplexy chains; detected clonally in 15/26 ERG+ prostate tumors as an early progression event PMID:23622249
  • TMPRSS2–ERG interstitial deletion fusion detected in MSK-PCa1 (non-expressed, AR-negative) and MSK-PCa3 (expressed) prostate cancer cell lines; models available for functional in vitro study PMID:25201530
  • EWSR1-ERG fusion in 9/112 Ewing sarcoma WGS discovery-cohort tumors; ETS-family fusion partner of EWSR1; three EWSR1-ERG-fused cases also showed chr 21/22 chromothripsis PMID:25223734
  • Recurrent ETS fusion (majority of ETS fusions involve ERG) in 56% of mCRPC cases PMID:26000489
  • Most common ETS fusion in primary prostate cancer (46%); TMPRSS2-ERG dominant; ERG-fusion-positive tumors split into low-methylation and hypermethylated epigenetic subclusters; co-occurs preferentially with PTEN deletion PMID:26544944
  • Mentioned in study PMID:26855148
  • TMPRSS2-ERG fusion status was 100% concordant across metastases within individual mCRPC patients by FISH (53 tumors, 13 men) and 94% concordant (32/34 men) by array CGH in a rapid-autopsy cohort PMID:26928463
  • Focal RAG-mediated 21q22.3 deletions in 55.6% of DUX4/ERG B-ALL cases (most commonly exons 3-7 or 3-9 of NM_182918.3); expression of a novel dominant-negative isoform ERGalt from non-canonical exon 6 alt (driven by DUX4 binding); NRAS-G12D cooperated with ERGalt to sustain lymphoid colony replating in Arf-/- mouse cells PMID:27776115
  • TMPRSS2-ERG fusion is the most common rearrangement in the MSK-IMPACT cohort (n=151) in PRAD; cryptic TMPRSS2 rearrangements detected in 23 additional PRAD cases consistent with chromoplexy PMID:28481359
  • TMPRSS2-ERG fusion cited as a canonical somatic prostate-cancer fusion in background context; cross-referenced to prior work on 17q12/HNF1B but not directly assayed in the NOL10/rs4519489 eQTL study PMID:28927585.
  • ERG is confirmed as an established driver in prostate cancer via TMPRSS2-ERG fusions; metastasis-vs-primary enrichment was quantified in the 1,013-patient WES cohort; ERG/TMPRSS2 fusions are confirmed among the set of established drivers including TP53, AR, PTEN, RB1, FOXA1, APC, BRCA2, and SPOP PMID:29610475.
  • TMPRSS2-ERG is the most-recurrent intra-cancer fusion overall in the TCGA pan-cancer fusion landscape (38.2% of PRAD samples, 205 samples flagged druggable); the fusion yields modest neoantigen yield in only a small subset of carriers PMID:29617662.

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • Mutually exclusive with MSI-H/dMMR status in prostate cancer PMID:38949888.
  • ERG fusion restricted to AR-expressing adenocarcinoma PDX models; absent in NEPC PMID:38488813.

Therapeutic relevance

  • ERG fusion-positive tumors appear to follow a distinct oncogenic pathway from MSI-H/dMMR prostate cancer, which has implications for immune checkpoint blockade eligibility PMID:38949888.

Open questions

  • Whether TMPRSS2-ERG fusion status predicts response to any specific therapy remains unresolved PMID:38488813.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26855148

This page was processed by wiki-cli on 2026-05-14. - PMID:26928463

This page was processed by wiki-cli on 2026-05-14. - PMID:27776115

This page was processed by entity-page-writer on 2026-05-15. - PMID:28481359

This page was processed by wiki-cli on 2026-05-15. - PMID:28927585

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15.