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The commonest genetic change in prostate cancer, present in roughly half of tumours. Nothing treats it and it does not make the cancer more dangerous; it is useful mainly for recognising that two samples came from the same tumour.
A fusion joining the 5' untranslated region of the androgen-responsive gene TMPRSS2 to an ETS transcription factor, usually ERG, found by looking for outlier expression and confirmed in 23 of 29 samples by fluorescence in situ hybridisation (Tomlins 2005). Frequency depends on the assay as much as on the population: cBioPortal structural variants give ERG rearrangement in 152 of 333 (45.6%) in prad_tcga_pub, matching the 46% the TCGA paper reports, and 203 of 494 (41.1%) in prad_tcga_pan_can_atlas_2018, against 24 to 26% in the MSK-IMPACT panel cohorts, where the breakpoint introns have to be baited to be seen. Counting all ETS fusions together (ERG, ETV1, ETV4, ETV5, FLI1) gives 224 of 494 (45.3%) in the TCGA PanCancer deposit and 172 of 444 (38.7%) in prad_su2c_2019. Ancestry moves it further: in 65 treatment-naive Chinese prostate cancers the fusion rate was low and CHD1 deletion high (Ren 2018), with 4 of 65 ERG rearrangements in the deposit. The prognostic answer is clear and negative: in 1,180 men followed a median of 12.6 years, ERG overexpression carried a hazard ratio of 0.99 for biochemical recurrence and 0.93 for lethal disease, and a meta-analysis over 48 further studies found risk ratios of 1.00 and 0.99 (Pettersson 2012).
In plain words · ERG (Transcriptional regulator ERG) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Prostate cancer, Non-Hodgkin lymphoma and 4 more.
Finding this change is common and it is not bad news. It does not make prostate cancer more likely to come back or to spread, and no treatment is chosen because of it. Its main practical use is to confirm that a deposit found elsewhere in the body came from the prostate.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
Detection of a rearrangement joining TMPRSS2, or another androgen-responsive partner such as SLC45A3, to ERG or another ETS family gene, by RNA sequencing, by a DNA panel that baits the breakpoint introns, by fluorescence in situ hybridisation, or inferred from nuclear ERG protein by immunohistochemistry.
“By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1.”
Tomlins et al., Science 2005No approval uses this readout as a threshold. It is defined by Pettersson et al., Cancer Epidemiol Biomarkers Prev 2012: the TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes.
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
It is the reason a prostate cancer fusion frequency quoted without an ancestry is unsafe. In this cohort the founder event that defines almost half of Western tumours is uncommon, and the fusion-negative, CHD1-deleted route dominates instead.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
It is the definitive negative result for the commonest genomic alteration in this disease. A man told his tumour carries the TMPRSS2-ERG fusion should be told plainly that it does not make his cancer more dangerous.
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.
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