{"entity":{"id":"tmprss2-erg-fusion","kind":"biomarker","name":"TMPRSS2-ERG fusion (and the other ETS rearrangements)","aka":["TMPRSS2-ERG","TMPRSS2:ERG","ERG rearrangement","ETS fusion","ERG fusion","ERG positive","ETS-positive prostate cancer","TMPRSS2-ETV1"],"tldr":"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.","summary":"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).","asOf":"2026-09-25","links":[{"label":"Tomlins et al., Science 2005: recurrent fusion of TMPRSS2 to ERG or ETV1 in prostate cancer (29 samples by fluorescence in situ hybridisation)","url":"https://doi.org/10.1126/science.1117679"},{"label":"Pettersson et al., Cancer Epidemiol Biomarkers Prev 2012: TMPRSS2-ERG, ERG expression and outcome in a 1,180-man cohort and a meta-analysis of 48 studies","url":"https://doi.org/10.1158/1055-9965.EPI-12-0042"},{"label":"cBioPortal study prad_tcga_pub (TCGA, Cell 2015; the 333 primary tumours of the published molecular taxonomy)","url":"https://www.cbioportal.org/study/summary?id=prad_tcga_pub"}],"tags":["biomarker","prostate"],"related":["spop-mutation"],"cancers":["prostate"],"sections":[],"technologies":["cytogenetics-fish","rna-seq","histopathology-ihc","cgp"],"targets":["erg","etv1","tmprss2","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","ar-signaling","transcription-addiction"],"terms":["gene-fusion","fish","ihc","driver-mutation","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tomlins-tmprss2-ets-fusion-science-2005","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012","paper-ren-chinese-prostate-whole-genome-eur-urol-2018"],"journals":[],"dependsOn":[],"notes":[],"target":"erg","measurement":"sequencing-variant","scoringRule":{"text":"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.","quote":"By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1.","source":"https://doi.org/10.1126/science.1117679","sourceLabel":"Tomlins et al., Science 2005"},"thresholds":[],"definedBy":{"label":"Pettersson et al., Cancer Epidemiol Biomarkers Prev 2012: the TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes","url":"https://doi.org/10.1158/1055-9965.EPI-12-0042"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"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."},"route":"/biomarkers/tmprss2-erg-fusion/","neighbours":{"biomarker":[{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"}],"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"erg","kind":"target","name":"ERG","route":"/targets/erg/"},{"id":"etv1","kind":"target","name":"ETV1","route":"/targets/etv1/"},{"id":"tmprss2","kind":"target","name":"TMPRSS2","route":"/targets/tmprss2/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"biochemical-recurrence","kind":"term","name":"Biochemical recurrence (BCR)","route":"/terms/biochemical-recurrence/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"paper":[{"id":"paper-tomlins-tmprss2-ets-fusion-science-2005","kind":"paper","name":"Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer","route":"/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012","kind":"paper","name":"The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis","route":"/key-papers/paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012/"},{"id":"paper-ren-chinese-prostate-whole-genome-eur-urol-2018","kind":"paper","name":"Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression","route":"/key-papers/paper-ren-chinese-prostate-whole-genome-eur-urol-2018/"}]}}