TMPRSS2

Overview

TMPRSS2 is a serine protease gene that is the most common 5’ fusion partner for ETS transcription factors (most frequently ERG) in prostate cancer, producing the canonical TMPRSS2-ERG oncogenic fusion driven by androgen signaling.

Alterations observed in the corpus

  • TMPRSS2-ERG fusions were identified in 13 prostate cancer PDX models, and TMPRSS2-ETV4 fusions in 2 models, in the MDA PCa PDX series (n=37 models); ERG is overexpressed when fused with TMPRSS2 in AR-expressing models PMID:38488813.
  • TMPRSS2-ERG fusions were depleted in MSI-H/dMMR prostate cancer (3%) vs. TMB-H/MSS (12%) and TMB-L/MSS controls (p=0.015), suggesting distinct oncogenic pathways in hypermutant prostate cancer PMID:38949888.
  • Gene fusion partner (TMPRSS2-ERG) identified as the most common structural rearrangement in prostate cancer integrative genomic profiling of 218 tumors PMID:20579941
  • TMPRSS2-ERG ETS rearrangements present in up to 50% of prostate cancers; mutually exclusive with SPOP mutations, suggesting distinct early oncogenic pathways PMID:22610119
  • Recurrent TMPRSS2-ERG gene fusion identified in prostate cancer WES of 112 tumors (Michigan cohort) PMID:22722839
  • TMPRSS2-ERG recurrent androgen-regulated fusion via 21q intronic deletion; arose within chromoplexy chains in 15/26 ERG+ prostate cancer cases; observed clonally early in tumor progression PMID:23622249.
  • TMPRSS2-ERG interstitial deletion fusion present in MSK-PCa1 (non-expressed, AR-negative line) and MSK-PCa3 (expressed); enables modeling of the most common fusion in prostate cancer across distinct AR-pathway contexts PMID:25201530
  • Dominant androgen-regulated 5’ fusion partner in primary prostate cancer (PRAD); TMPRSS2-ERG is the most common ETS fusion (46%) PMID:26544944
  • TMPRSS2–ERG fusion concordance between adenocarcinoma and neuroendocrine foci of mixed tumors cited as evidence supporting a common cell of origin in CRPC-NE PMID:26855148
  • TMPRSS2-ERG fusion status 100% concordant across metastases by FISH (53 tumors, 13 men) and 94% concordant by array CGH (32/34 men) in mCRPC rapid-autopsy cohort PMID:26928463
  • TMPRSS2-ERG rearrangement is the most common rearrangement detected across 62 principal tumor types in MSK-IMPACT (n=10,336); observed in 151 prostate adenocarcinoma (PRAD) cases; cryptic TMPRSS2 rearrangements consistent with chromoplexy detected in 23 additional PRAD cases PMID:28481359
  • Cited as canonical somatic prostate-cancer fusion gene (TMPRSS2-ERG) in background context; not directly assayed in this eQTL study of rs4519489-USF1-NOL10 axis PMID:28927585
  • TMPRSS2-ERG fusions confirmed as an established driver in the SU2C/PCF 1,013-sample prostate cancer cohort; metastasis-vs-primary enrichment quantified PMID:29610475
  • TMPRSS2-ERG is the most-recurrent intra-cancer fusion overall (38.2% of PRAD, 205 samples flagged druggable); predicted fusion-derived neoantigens were highest for TMPRSS2-ERG among all PRAD fusions though only in a small subset PMID:29617662

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • TMPRSS2-ERG fusion is mutually exclusive with other ETS fusions; depleted in MSI-H/dMMR tumors suggests mutual exclusivity with hypermutation-driven oncogenesis in prostate cancer PMID:38949888.

Therapeutic relevance

  • AR-signaling drives TMPRSS2 promoter activity; TMPRSS2-ERG fusion prevalence is linked to AR-expressing adenocarcinoma models; androgen deprivation therapy may suppress fusion expression PMID:38488813.

Open questions

  • The mechanism by which TMPRSS2-ERG fusions are depleted in MSI-H/dMMR prostate cancer (whether MMR deficiency prevents the chromosomal rearrangement or selects for alternative drivers) is not resolved in the corpus PMID:38949888.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:20579941

This page was processed by crosslinker on 2026-05-14. - PMID:22610119

This page was processed by crosslinker on 2026-05-14. - PMID:22722839

This page was processed by crosslinker on 2026-05-14. - PMID:23622249

This page was processed by crosslinker on 2026-05-14. - PMID:25201530

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: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.