# Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer

Source: https://onco.cc/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/  
OnCo record `paper-tomlins-tmprss2-ets-fusion-science-2005` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Gene fusions were thought to be a feature of leukaemias, not common solid cancers. This study found one in prostate cancer that joins a switch controlled by testosterone to a growth gene, and found it in most of the tumours it looked at.

## Summary

Scott Tomlins, Arul Chinnaiyan and colleagues at Michigan used a bioinformatics method that looks for genes expressed at extreme levels in a minority of samples, identified ERG and ETV1 as outliers in prostate cancer, and then found recurrent fusions joining the 5 prime untranslated region of TMPRSS2 to one or the other.

The mechanism is elegant and specifically prostatic: TMPRSS2 is androgen-responsive, so the fusion puts an ETS transcription factor under the control of the hormone that the prostate is bathed in. It was the first recurrent chromosomal rearrangement found in a common carcinoma, and it broke the assumption that fusions belong to haematological cancers. Twenty years later it defines the largest molecular subtype of prostate cancer and has still produced no drug, which is the honest state of the finding.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Also known as: Tomlins 2005; TMPRSS2-ERG fusion; TMPRSS2-ETV1
- Tags: prostate-evidence
- Journal: Science
- Year: 2005
- DOI: 10.1126/science.1117679
- Authors: Tomlins SA, Rhodes DR, Perner S, et al.
- Findings: Recurrent gene fusions of the 5 prime untranslated region of TMPRSS2 to ERG or ETV1 were identified in prostate cancer tissues with outlier expression.; Fluorescence in situ hybridisation demonstrated rearrangements in ERG or ETV1 in 23 of 29 prostate cancer samples.; Cell line experiments suggest the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members.; The finding established that recurrent chromosomal rearrangements, previously characterised mainly in haematological malignancies, occur in a common carcinoma.
- What it means: The most common single molecular event in prostate cancer, present in roughly half of tumours in most series, and the reason prostate cancer is classified by fusion status. It is also a standing reminder that finding the driver and drugging it are different problems: no ETS-directed therapy has reached the clinic.
- Caveats: 23 of 29 samples is a discovery cohort, not a prevalence estimate; large series put ERG rearrangement at roughly half of prostate cancers and lower in men of African ancestry.; Fusion status has repeatedly failed to predict prognosis consistently across cohorts.; Transcription factors remain difficult to drug; two decades on, ETS fusion status changes classification and not treatment.

## Sources

- Science 2005: https://doi.org/10.1126/science.1117679
- PubMed: https://pubmed.ncbi.nlm.nih.gov/16254181/

## Connected records

- key papers: [Integrative genomic profiling of human prostate cancer](https://onco.cc/key-papers/paper-taylor-integrative-genomic-profiling-cancer-cell-2010/), [TCGA: the molecular taxonomy of primary prostate cancer](https://onco.cc/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/)
- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- cancers: [Localised prostate cancer, high and very high risk](https://onco.cc/cancers/prostate-high-risk/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [ERG](https://onco.cc/targets/erg/), [ETV1](https://onco.cc/targets/etv1/), [TMPRSS2](https://onco.cc/targets/tmprss2/)
- institutions: [University of Michigan Rogel Cancer Center](https://onco.cc/institutions/michigan-rogel/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Prostate cancer (KEGG map)](https://onco.cc/pathways/prostate-cancer-signalling/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene fusion](https://onco.cc/terms/gene-fusion/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- people: [Arul M. Chinnaiyan](https://onco.cc/people/arul-chinnaiyan/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- journals: [Science](https://onco.cc/journals/science/)
- biomarkers: [TMPRSS2-ERG fusion (and the other ETS rearrangements)](https://onco.cc/biomarkers/tmprss2-erg-fusion/)

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