ERG (v-ets erythroblastosis virus E26 oncogene like (avian))

2010-11-01   Roopika Menon , Martin Braun , Sven Perner 


Atlas Image
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.


Atlas Image
ERG gene locus on the q-arm of chromosome 21 (21q22.2) spanning from 39751949 to 40033704 (according to UCSC genome browser, Feb. 2009 GRCh37/hg19, and Ensemble, Aug. 2010).


The ERG gene belongs to the erythroblast transformation-specific (ETS) family of transcriptions factors. The ERG gene (ETS related gene 1) is located on chromosome 21, and consists of 17 exons, approximately 300 kb DNA in length.


The ERG gene forms 20 known transcripts (ranging from 560 to 5034 bp in length), amongst which 15 are coding for proteins, and 5 are non-coding. 8 alternative splice variants are known.


No observed pseudogenes.



Amongst the 20 known transcripts of the ERG gene, 15 are protein coding. The 15 proteins range from 171 to 486 amino acids in length, and up to 55 kDa in weight.


On the protein level, ERG is mainly expressed in the nucleus and is rarely seen in the cytoplasm. Basically, in the GNF SymAtlas database, major ERG expression was found to be in CD34+ cells (that include both hematopoietic stem cells and endothelial cells). In detail, ERG is reported to be expressed during early T and B cell development, and down-regulated in later stages of B and T cell differentiation. Also, ERG is expressed in platelets, megakaryoblastic cell lines, primary megakaryoblastic leukemia (AMKL or M7-AML) in Down syndrome patients. Furthermore, ERG is strongly expressed in ERG gene rearranged prostate tissue (both in prostatic cancer tissue and adjacent prostatic intraepithelial neoplasia lesions). Of note, using immunohistochemistry, ERG expression is regularly observed in lymphocytes and small blood vessels.


Predominantely nuclear and rarely cytoplasmic.


The ERG protein is a member of the ETS-family and is known to bind to purine-rich sequences. ERG and other members of the same family are downstream regulators of mitogenic signal transduction pathways. They are key regulators of embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis. At the DNA level, isoforms of ERG are known to regulate methylation. Further, ERG is required for platelet adhesion to the subendothelium, inducing vascular cell remodeling. Moreover, hematopoesis, as well as the differentiation and maturation of megakaryocytic cells are regulated by ERG. Overexpression of the ERG protein is suggested to aid in forming solid tumors. However, the exact molecular mechanisms of ERG as a transcription factor are still unknown.


A member of the ETS transcription factors, most homologous to FLI1.



No known mutations.

Implicated in

Entity name
Ewings sarcoma
The prognostic relevance of an ERG gene fusion or an ERG overexpression in Ewings sarcoma (EWS-ETS fusion type) is yet to be determined. So far, no prognostic relevance could be shown.
Hybrid gene
If a gene fusion occurs in Ewings sarcoma, most frequently it is a fusion of EWS to FLI-1 (in app. 85% of cases) or ERG (in app. 10% of cases). Other ETS genes rarely serve as EWS gene fusion partners (in app. 5% of cases).
Fusion protein
The EWS gene fuses with the carboxyl terminal of ERG containing the ETS DNA binding domain of ERG. Therefore, the resulting fusion protein deregulates a large number of genes by so far poorly defined mechanisms.
In a transgenic mouse model expression of the EWS-ERG in lymphoid progenitors induced T-cell leukemia.
Entity name
Several studies suggest a poorer prognosis for FUS-ERG gene fusion positive AML as compared to non-fused AML. Moreover, an ERG overexpression, not necessarily due to the FUS-ERG gene fusion, predicts an increased relapse risk and shorter survival in AML patients. However, the exact contribution of ERG overexpression to myeloid leukemiogenesis and progression is still unknown.
Hybrid gene
In the FUS-ERG gene fusion, the FUS gene fuses with the carboxyl terminal of ERG containing the ETS DNA binding domain of ERG. Of note, in a single case, a gene fusion of ERG with the myeloid ELF-like factor 1 (ELF4) was detected.
The FUS-ERG fusion protein helps in activating the oncogenic activity of transcription factors.
Entity name
Prostate cancer
The body of literature is controversial about the prognostic relevance of ERG rearrangements in prostate cancer. Some studies reported an association of the ERG rearrangement with adverse clinical parameters (i.e. time to prostate cancer specific death and the development of hormone-refractory metastasis). On the other hand, some studies demonstrated an association of ERG rearrangement with parameters of more favourable outcome, such as lower Gleason score, stage, volume, better overall survival, or late biochemical recurrence. Interestingly, a subset of studies without any such association was reported as well.
Hybrid gene
In approximately 50% of prostate cancers, the ERG gene is rearranged, i.e. fused to another gene. In case of a rearrangement, TMPRSS2 is the ERG 5 fusion partner in the vast majority of cases (app. 85%). Other known, but rarely occurring ERG fusion partners include NDRG1, SLC45A3, and HERPUD1. The ERG gene rearrangement either occurs due to a deletion, or an insertion.
Atlas Image
Schematic displaying ERG rearrangement status (via FISH) in prostate cancer. The red-labelled centromeric and the green-labelled telomeric probes span the ERG locus on chromosomes 21. If a break-apart occurs, the green signal is either lost (ERG rearrangement through deletion) or translocated (ERG rearrangement through insertion). An ERG break-apart as determined by FISH accounts for a fusion of ERG mainly with TMPRSS2 but also with other 5 fusion partners such as SLC45A3, HERPUD1, or NDRG1. A: Both alleles with wild type (wt) ERG. B: One allele with ERG rearrangement through deletion (single red signal) and the other allele with wt ERG (yellow signal). C: One allele with ERG rearrangement through insertion (separated red and green signal) and the other allele with wt ERG (yellow signal).
Fusion protein
An ERG gene rearrangement in prostate cancer mainly results in an androgen dependant ERG overexpression.
In-vitro models complement that over expression of truncated ERG and various TMPRSS2-ERG isoforms increase cell migration and invasion. In-vivo recapitulation of ETS fusions by prostate specific expression of truncated ERG in mice resulted in the development of PIN but not carcinoma. Subsequent work on transgenic TMPRSS2-ERG mice develop PIN progressing to invasive cancer, but only in the context of PI3-kinase pathway activation. TMPRSS2-ERG-positive human tumors are also enriched for PTEN loss, suggesting cooperation in prostate tumorigenesis.
Entity name
Acute lymphoblastic leukemia (ALL)
Overexpression of ERG was shown to be a risk factor in adult T-ALL. ALL patients with ERG overexpression were four times more likely to fail long-term recurrence free survival, indicating inferior survival.
Studies assessing ERG overexpression in ALL have shown that due to the involvement of ERG in T-cell development, it may have an oncogenic potential.
Even though ERG is highly considered to be oncogenic in AMKL, no prognostic relevance has been determined.
ERG was found to be expressed megakaryoblastic leukemic cell lines and in primary leukemic cells from DS patients. Moreover, in mouse models, expression of ERG drove megakaryopoiesis and lead to a rapid development of aggressive leukemia.
Entity name
Alzheimers disease (AD)
ERG has been linked to AD, due to an ERG protein overexpression as compared to control patients. This is further supported by experiments conducted on patients suffering from Down syndrome, who gradually develop AD-like symptoms, linked to ERG overexpression.
Entity name
Down syndrome (DS)
DS is associated with trisomy of the chromosome 21, where the ERG gene is located. The trisomy is considered to be responsible for an ERG overexpression. In a DS mouse model, an induced functional disomy of the ERG allele corrects some pathologic features of the disease, including myeloproliferation and progenitor cell expansion, suggesting a pathogenic effect of trisomy driven ERG overexpression.
Entity name
ERG involvement in endothelial development
ERG has been reported to regulate genes involved in chondrogenesis and angiogenesis and functions as a modulator of endothelial cell differentiation. In an in-vitro study, the decrease of the ERG protein follows a reduction in endothelial cell proliferation and vascular tube formation. In human umbilical vein endothelial cell lines, vascular endothelial growth factor (VEGF) was seen to significantly up-regulate ERG expression. Controversially, on the other hand, ERG expression was shown to inhibit responsiveness to the VEGF receptor in a Down Syndrome mouse model.
Entity name
ERG involvement in lymphoid development
ERG was reported to be expressed in during early T and B cell development, and to be down-regulated in later stages of B and T cell differentiation. In detail, the ERG protein modulates the maturation of lymphoid cells. Interestingly, ERG overexpression is associated with T-ALL.


Atlas Image


Pubmed IDLast YearTitleAuthors
164485442006At the crossroads: diverse roles of early thymocyte transcriptional regulators.Anderson MK et al
169545202006High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults.Baldus CD et al
150071642004Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP, ETS2, and ERG genes.Baldus CD et al
200685662010Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts.Barwick BG et al
197162272010Expression of the androgen-regulated fusion gene TMPRSS2-ERG does not predict response to endocrine treatment in hormone-naïve, node-positive prostate cancer.Boormans JL et al
193961682009Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.Carver BS et al
205703492011The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia.Coskun E et al
206973432010Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and progenitor cell differentiation in Down's syndrome.De Vita S et al
85109311993New human erg isoforms generated by alternative splicing are transcriptional activators.Duterque-Coquillaud M et al
195554382010BAALC and ERG expression in acute myeloid leukemia with normal karyotype: impact on prognosis.Eid MA et al
206939822010ERG rearrangement is present in a subset of transition zone prostatic tumors.Falzarano SM et al
80403011994EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations.Giovannini M et al
206711892010Identification of a cell of origin for human prostate cancer.Goldstein AS et al
207135282010FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells.Gupta S et al
206019562010Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements.Haffner MC et al
205460202010ETS-related gene ERG expression in AML patients is significantly associated with NPM1 mutation status.Hämäläinen M et al
202205132010ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia.Han B et al
204324692010Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis.Heo SH et al
113121052001Selective expression of erg isoforms in human endothelial cells.Hewett PW et al
116806872001The role of ERG (ets related gene) in cartilage development.Iwamoto M et al
206337682010Complex rearrangement of chromosomes 1, 7, 21, 22 in Ewing sarcoma.Jinawath N et al
193961672009Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis.King JC et al
92425521997Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.Kong XT et al
204799322010ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.Kunderfranco P et al
208084442010VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2.Le Bras A et al
203086732010Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial.Le Deley MC et al
208008812010TMPRSS2-ERG gene fusion and clinicopathologic characteristics of Korean prostate cancer patients.Lee K et al
204423002010Association of SPINK1 expression and TMPRSS2:ERG fusion with prognosis in endocrine-treated prostate cancer.Leinonen KA et al
185003452008The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells.Loughran SJ et al
208789522011TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients.Magi-Galluzzi C et al
206173392010CD99-positive large cell neuroendocrine carcinoma with rearranged EWSR1 gene in an infant: a case of prognostically favorable tumor.Malone VS et al
205161222010Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis.Mao X et al
162759342005Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study.Marcucci G et al
117193712001Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation.McLaughlin F et al
163031802006ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25-26;q22).Moore SD et al
200075482010Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome.Ng AP et al
206206042010Two childhood cases of acute leukemia with t(16;21)(p11.2;q22): second case report of infantile acute lymphoblastic leukemia with unusual type of FUS-ERG chimeric transcript.Oh SH et al
125595632003Molecular biology of the Ets family of transcription factors.Oikawa T et al
152987232004ETS transcription factors: possible targets for cancer therapy.Oikawa T et al
206761252010A previously unrecognized promoter of LMO2 forms part of a transcriptional regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic leukaemia patients.Oram SH et al
146933722004Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison with the region of conserved synteny on mouse chromosome 16.Owczarek CM et al
206519882010Antibody-based detection of ERG rearrangement-positive prostate cancer.Park K et al
200183532010ERG rearrangement metastasis patterns in locally advanced prostate cancer.Perner S et al
206872252010An in vitro model for preclinical testing of endocrine therapy combinations for prostate cancer.Pfeiffer MJ et al
161409242005The proto-oncogene ERG in megakaryoblastic leukemias.Rainis L et al
205352112010Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome.Reynolds LE et al
201600632010Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer.Rice KR et al
203035382010Clinical implications of TMPRSS2-ERG gene fusion expression in patients with prostate cancer treated with radical prostatectomy.Rubio-Briones J et al
194872852009ERG is a megakaryocytic oncogene.Salek-Ardakani S et al
206367942010ERG rearrangement in small cell prostatic and lung cancer.Scheble VJ et al
208608282010Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation.Schulz WA et al
204240122010Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer.Stott SL et al
205799412010Integrative genomic profiling of human prostate cancer.Taylor BS et al
194096902009ETS gene fusions in prostate cancer: from discovery to daily clinical practice.Tomlins SA et al
2014752520101{alpha},25-Dihydroxyvitamin D3 inhibits growth of VCaP prostate cancer cells despite inducing the growth-promoting TMPRSS2:ERG gene fusion.Washington MN et al
205172972010Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo.Wei GH et al
208879582010Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators.Wilson NK et al
120868722002Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.Yeoh EJ et al
204785272010An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.Yu J et al
203086692010Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group.van Doorninck JA et al
162370842005Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression.van Zelm MC et al

Other Information

Locus ID:

NCBI: 2078
MIM: 165080
HGNC: 3446
Ensembl: ENSG00000157554


dbSNP: 2078
ClinVar: 2078
TCGA: ENSG00000157554


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
204785272010An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.337
193392692009Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer.191
199331092009Induced chromosomal proximity and gene fusions in prostate cancer.155
185059692008Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer.130
185198262008Molecular genetics of successful smoking cessation: convergent genome-wide association study results.130
206519882010Antibody-based detection of ERG rearrangement-positive prostate cancer.126
238170212013ETS factors reprogram the androgen receptor cistrome and prime prostate tumorigenesis in response to PTEN loss.120
207135282010FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells.111
227050542012Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.104
227367902012The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis.102


Roopika Menon ; Martin Braun ; Sven Perner

ERG (v-ets erythroblastosis virus E26 oncogene like (avian))

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version:

Historical Card

2006-08-01 ERG (v-ets erythroblastosis virus E26 oncogene like (avian)) by  Liat Rainis-Ganon,Shai Izraeli 

Head, Research section, Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621