Recurrent fusion of tmprss2 and ets transcription factor. Although the tmprss2 erg gene fusion appears to be a suitable diagnostic biomarker, the prognostic implications of this gene fusion are still unclear. Seven of 19 of the xenografts contained the tmprss2. We identified the fusion gene tmprss2erg by reversetranscriptase polymerase chain reaction rtpcr in 4055 carcinomas 72%. Transmembrane protease, serine 2 and v ets erythroblastosis virus e26 homolog tmprss2 erg gene fusions are the common molecular signature of prostate cancer. The studies on tmprss2erg gene fusions have seldom been performed at the protein level, primarily due to the lack of highquality antibodies or an antibodyindependent method that is sufficiently sensitive for detecting the truncated erg protein products resulting from tmprss2erg gene fusions and alternative splicing. Both genes are located within 3 mb on chromosome 21 and the most common mechanism. Early detection of clinically significant prostate cancer. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ets genes erg and etv1 in prostate cancer have been published.
Centre for personalized nanomedicine, australian institute for bioengineering and nanotechnology aibn, the university of queensland, qld 4072, australia. The tmprss2ets fusion prostate cancers comprise 5070% of the prostatespeci. Tmprss2ets fusion transcript that encodes a nearly. Obesity and prostate cancer risk according to tumor. Immunohistochemistry and rtpcr were employed to detect tmprss2. Colorimetric tmprss2erg gene fusion detection in prostate. Although tremendous advances have been made in unraveling various facets of tmprss2erg. The gene view histogram is a graphical view of mutations across tmprss2. Rearrangements between the androgen regulated tmprss2 gene promoter and the etsrelated erg gene result in tmprss2erg fusion transcripts that have been found in approximately half of prostate cancer cases in the western world. Jan, 2014 activation of the erg oncogene represents an early event in preneoplastic to neoplastic transition during prostate tumorigenesis 24.
Gene fusions between tmprss2 and ets family genes in prostate cancer. Tmprss2 erg fusion gene is the most frequent, present in 40% 80% of prostate cancers in humans. Since then, tmprss2 erg fusion gene related studies had become the hotspot of pca research. Targeting ets gene fusions in cancer clinical cancer research. The studies on tmprss2 erg gene fusions have seldom been performed at the protein level, primarily due to the lack of highquality antibodies or an antibodyindependent method that is sufficiently sensitive for detecting the truncated erg protein products resulting from tmprss2 erg gene fusions and alternative splicing. Erg fusion subtypes have been uncovered, ranging from chromosomal rearrangements to fusion transcripts 10, 1215. Morphological features of tmprss2erg gene fusion prostate cancer. Fusion transcripts arising from translocations of a prostatespecific tmprss2 gene with oncogenic ets factors, erg, etv1, or etv4, were recently identified in up to half of all human prostate cancers 1, 2.
Although tremendous advances have been made in unraveling various facets of tmprss2 ergpositive prostate cancer. Transgenic mice expressing the erg gene fusion product under androgenregulation. Tmprss2 is an androgenregulated gene that is preferentially expressed in the prostate. The somatic fusion of tmprss2 to ets oncogenes is a common event in prostate cancer pca. Erg gene fusion is common in prostate cancer, while its functional role is not fully understood. Fusion of the prostatespecific and androgenregulated transmembraneserine protease gene tmprss2 with the erythroblast transformationspecific ets family members is the most common genetic alteration in prostate cancer. Our study demonstrates that the detection of ets fusion gene by rtpcr is feasible on formalinfixed and paraffinembedded samples. Gene expression alterations in prostate cancer representing an opportunity to refine early detection include overexpression of pca3, a noncoding rna, 812 and aberrant tmprss2. Tmprss2erg expression predicts prostate cancer survival and. Activation of the erg oncogene represents an early event in preneoplastic to neoplastic transition during prostate tumorigenesis 24. Erg fusion may also become an important diagnostic marker as it is highly specific for prostate cancer and detectable in urine. We have previously conducted a genomewide linkage analysis in tmprss2 erg fusion positive pca families, revealing potential susceptibility loci on.
Tmprss2 fusions with oncogenic ets factors in prostate cancer. Fd and the department of defense prostate cancer program kf. Statistical analysis was performed to look for signi. Detection of the tmprss2 ets fusion gene in prostate carcinomas. A fusion gene is a hybrid gene formed from two previously independent genes.
Erg was highly expressed in the nuclei of endothelial cells of vessels and weak cytoplasmic staining was occasionally observed. The present study aimed to investigate the significance of the tmprss2. Consequences of tmprss2erg fusion in prostate cancer. Dna binding domain of an ets family member, such as erg t21. Tmprss2 gene genecards tmps2 protein tmps2 antibody. Erg gene fusion is a frequent, early event in the genesis of prostate cancer, as confirmed by the new data from rajput et al. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer.
Obesity and prostate cancer risk according to tumor tmprss2. Novel recurrent gene fusions between the androgenregulated gene tmprss2 and the ets family members erg, etv1, or etv4 have been recently identified as a common molecular event in prostate cancer. They find that in t2e tumors, there is a distinct regulatory landscape. Erg fusion transcript and showed fused signals by fish. They also overexpressed erg, as determined by the qrtpcr. Perner s1, schmidt fh, hofer md, kuefer r, rubin m. We have previously conducted a genomewide linkage analysis in tmprss2erg fusionpositive pca families, revealing potential. As such, fusion would result in a transcript containing exon 1 and. Tmprss2ets gene fusion in prostate cancer northwestern. Thus, these studies highlighted the potential of tmprss2 ets gene fusions to serve as a specific biomarker for the early. Translocations fusing the strong androgenresponsive gene, tmprss2, with erg or other oncogenic ets factors may facilitate prostate cancer development. Tmprss2erg fusion gene is specifically expressed in pca, involving the tmprss2 gene regulated by androgen and the oncogene erg that is a member of the ets family of transcription factors. The present study aimed to investigate the significance of. An early and common alteration is the gene fusion between the transmembrane protease serine 2 tmprss2 gene and the vets avian erythroblastosis virus.
However, the biological and clinical role of tmprss2 ets fusions in prostate cancer, especially in problematic prostate needle core biopsies, has not been rigorously. Mar 10, 2017 this idea has been brought into question by the finding of recurrent fusion of the androgenregulated tmprss2 gene to the ets transcription factors, particularly the erg gene, in the majority of prostate cancers prostate cancer. Predictive significance of tmrpss2 erg fusion in prostate. The integrated landscape of driver genomic alterations in glioblastoma. Because translocations involving ets family members are functionally redundant in oncogenic transformation, only one type of translocation is typically observed in each case of ewings sarcoma.
Among its related pathways are coregulation of androgen receptor activity and endometrial cancer. B, interphase nuclei of a stromal cell left and a prostate cancer gland right. It is a multifaceted and genomically complex disease. This creates an androgenregulated tmprss2ets fusion transcript that. Recurrent gene fusion between the androgenregulated gene tmprss2 and members of the ets transcription factor family, most commonly erg, are present in about 50% of prostate cancer cases. This idea has been brought into question by the finding of recurrent fusion of the androgenregulated tmprss2 gene to the ets transcription factors, particularly the erg gene, in the majority of prostate cancers prostate cancer. Application note quantstudio 3d digital pcr system detection. Tmprss2 fusions with oncogenic ets factors in prostate. Ets gene fusions in prostate cancer atlas of genetics. Application note quantstudio 3d digital pcr system. The presence of the tmprss2erg fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. Bioinformatics analysis of genes and micrornas located.
Erg is an oncogene that encodes a member of the erythroblast transformation. Fusion of the transmembrane protease, serine 2, gene tmprss2 and the erythroblast transformationspecific etsrelated gene erg, creating the tmprss2. These mutations are displayed at the amino acid level across the full length of the gene by default. Tmprss2erg fusion coopts master transcription factors. Early detection of clinically significant prostate cancer at. Most of the less frequent ets fusion partners are also androgenregulated and prostatespecific. However, the biological and clinical role of tmprss2ets fusions in prostate cancer, especially in problematic prostate needle core biopsies, has not been rigorously. Erg gene fusion, which occurs in more than 50% of prostate cancer cases 2, this gene fusion appears to be a suitable. Two ets transcription factors, erg and etv1, were identified as outliers in prostate cancer.
Crisprinduced tmprss2erg gene fusions in mouse prostate. It has been shown that gene fusions affecting ets transcription factors are common in prostate cancer. Rouzier c, haudebourg j, carpentier x, valerio l, amiel j, michiels jf, pedeutour f. Erg fusion identifies a subgroup of prostate cancers with a favorable prognosis outi r. Restrict the view to a region of the gene by dragging across the histogram to highlight the region of interest, or by using the sliders in the filters panel to the left. Predisposition for tmprss2erg fusion in prostate cancer.
Tmprss2erg expression predicts prostate cancer survival. Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the tmprss2ets gene fusion is the most common genetic aberration so far described in human malignancies. Prostate cancer is a gland tumor in the male reproductive system. Erg gene fusion edit tmprss2 proteins function in prostate carcinogenesis relies on overexpression of ets transcription factors, such as erg and etv1, through gene fusion. Tmprss2erg fusion gene is the most frequent, present in 40% 80% of prostate cancers in humans. Here, we explored the role of tmprss2erg gene fusion product using in vitro and in vivo model systems.
Dec 05, 2014 an early and common alteration is the gene fusion between the transmembrane protease serine 2 tmprss2 gene and the v ets avian erythroblastosis virus e26 oncogene homolog erg gene resulting in. Gene ontology go annotations related to this gene include serinetype endopeptidase activity and scavenger receptor activity. Comprehensive assessment of tmprss2 and ets family gene. Tmprss2etv4 fusion was identified with a prevalence of only 1. Based on a historical watchful waiting cohort, an association between tmprss2erg, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Abstract we explore noninvasive clinical applications of multiple disease. Erg gene fusion associated with lethal prostate cancer. Investigation of erg rearrangement in multifocal cap and corresponding metastases provides a glimpse of the potential biological impact of this aberration in the context of disease progression perner et al.
Interphase fish on ffpe tissue sections con firms tmprss2. Erg gene fusions in prostate cancer of west african. Nov 12, 2018 tmprss2 erg fusion gene is specifically expressed in pca, involving the tmprss2 gene regulated by androgen and the oncogene erg that is a member of the ets family of transcription factors. Although the tmprss2erg gene fusion appears to be a suitable diagnostic biomarker, the prognostic implications of this gene fusion are still unclear. The t2e gene fusion, formed by fusion of the transmembrane protease, serine 2, gene tmprss2 with the erythroblast transformationspecific ets related gene erg, is found in approximately 50% of prostate cancers and may characterize distinct molecular subtypes of prostate cancer with different etiologies. Showing 25 of 1,225 results for tmprss2 search time. Erg t2e gene fusion, is found in approximately 50% of prostate cancers. Here, we explored the role of tmprss2 erg gene fusion product using in vitro and in vivo model systems. Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the tmprss2 ets gene fusion is the most common genetic aberration so far described in human malignancies. Recurrent fusion of tmprss2 and ets transcription factor genes.
It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Presence of this fusion gene is a critical event in the development of prostate cancer. Tmprss2 encodes for a transmembrane serine protease and harbors androgenresponsive elements in the promoter region. Antibodyindependent targeted quantification of tmprss2erg. We identified the fusion gene tmprss2 erg by reversetranscriptase polymerase chain reaction rtpcr in 4055 carcinomas 72%. Tmprss2 etv4 fusion was identified with a prevalence of only 1. Diseases associated with tmprss2 include influenza and prostate cancer. Tmprss2 transmembrane serine protease 2 is a protein coding gene. Tmprss2erg gene fusions are the predominant molecular subtype of prostate cancer. Transmembrane protease, serine 2 and vets erythroblastosis virus e26 homolog tmprss2erg gene fusions are the common molecular signature of prostate cancer. To create organoids carrying a tmprss2 erg gene fusion at. Fusion genes have been found to be prevalent in all main types of human neoplasia.
Tmprss2 erg gene fusions are the predominant molecular subtype of prostate cancer. Erg gene fusions and pten deletions are the most common genomic aberrations in prostate cancer. The stromal cell is negative for fusion, confirmed by the presence of two juxtaposed red and green signals resulting in two yellow signals. Thus, these studies highlighted the potential of tmprss2ets gene fusions to serve as a specific biomarker for the early. The clusters were separated under these conditions, but better.
Several new strategies for therapeutically targeting ets fusions and their modulators have been identified and are currently being investigated. We identified recurrent gene fusions of the 5 untranslated region of tmprss2 to erg or etv1 in prostate cancer tissues with outlier expression. The tmprss2erg gene fusion is found in approximately half of all prostate cancers. Five morphological features were associated with tmprss2erg. B fusion involving exons 1 and 2 of the tmprss2 gene 3. Tmprss2 is an androgenresponsive gene and ar regulated expression of the tmprss2erg fusion gene plays an early role in prostate cancer development and progression as its presence is required for. Colorimetric tmprss2 erg gene fusion detection in prostate cancer urinary samples via recombinase polymerase amplification. Recently, multiple groups have confirmed the heterogeneity of ets gene fusion status as indicated with fish for tmprss2 or erg rearrangements between tumor foci in multifocal prostate cancers. Colorimetric tmprss2erg gene fusion detection in prostate cancer urinary samples via recombinase polymerase amplification. Erg expression, which results from a prostate cancerspecific chromosomal rearrangement on chromosome 21 that juxtaposes the 5. In this study, fluorescent in situ hybridization fish assays were used to assess. We hypothesized that defects in dna repair may lead to an increase of chromosomal rearrangements and thus to the occurrence of ets oncogene fusion. Role of the tmprss2erg gene fusion in prostate cancer ncbi. Mathieu lupien and colleagues analyze data from primary prostate tumors with and without tmprss2 erg t2e rearrangements.
Ets gene fusionpositive foci may arise independently and exhibit interfocal heterogeneity. So far, this is the only gene rearrangement in any of the most prevalent cancers. Antibodyindependent targeted quantification of tmprss2. Detection of tmprss2ets fusions by a multiprobe fluorescence.
Two xenografts lucap49 and lucap93 contained the rearrangement according to fish analysis but did not express erg or contain the fusion transcript. Erg gene fusion in human prostate cancers using bioinformatics tools. Transgenic mice expressing the erg gene fusion product under androgenregulation develop mouse prostatic intraepithelial neoplasia pin, a precursor lesion of prostate cancer. Introduction of the erg gene fusion product into primary or immortalized benign prostate epithelial cells induced an invasionassociated transcriptional program. The functional and prognostic significance of tmprss2erg is, however, not fully understood. Tmprss2 proteins function in prostate carcinogenesis relies on overexpression of ets transcription factors, such as erg and etv1, through gene fusion. Predisposition for tmprss2erg fusion in prostate cancer by. Role of the tmprss2erg gene fusion in prostate cancer. Detection of the tmprss2ets fusion gene in prostate. Tmprss2erg fusion, a common genomic alteration in prostate. Recurrent fusion of tmprss2 and ets transcription factor genes in prostate cancer. Although both translocation partners have been previously studied in prostate cancer 3, 4, the identification of a translocation between the two genes provides new. The fusion of tmprss2 with ets genes was recently reported by tomlins et al 1 as the first recurrent genomic alteration in prostate cancer and has been now confirmed by multiple independent groups.
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