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Urine Tmprss2: Erg Fusion Transcript As A Biomarker For

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Prospective Multicentre Evaluation of PCA3 and TMPRSS2-ERG Gene Fusions as Diagnostic and Prognostic Urinary Biomarkers for Prostate Cancer In this study, we analyzed the current role of urinary gene fusion transcripts involving v-ets erythroblastosis virus E26 oncogene homolog, commonly known as ERG, and the androgen-regulated gene transmembrane protease, serine 2 (TMPRSS2), as a biomarker for PCA. Used as a single marker, urinary TMPRSS2:ERG has low sensitivity but high specificity.

Diagnostic Biomarkers of Prostate Cancer

Knockout of the EXO5 gene enhances the frequency of TMPRSS2-ERG gene ...

By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer.

Purpose This study aims to analyze prostate cancer antigen 3 (PCA3) as well as transmembrane serine protease 2:ERG (TMPRSS2:ERG) for diagnosing and serving as urine biomarkers in predicting prostate cancer incidences. In 2006, the TMPRSS2-ERG gene fusion transcripts were successfully detected in urine samples (48). This urine test had a sensitivity of 37% and a specificity of 93% for the prediction of PCa on prostate biopsy (7).

Measurements Urine was collected after attentive digital rectal exam (DRE) and coded to blind group allocation for laboratory test. RNA from urine sediments was analyzed using a panel of four TMPRSS2:ERG fusion markers with

Urine TMPRSS2: ERG Fusion Transcript as a Biomarker for Prostate Cancer: Literature Review. Sanguedolce F, Cormio A, Brunelli M, D’Amuri A, Carrieri G, Bufo P, Cormio L

Schematic representation of rapid and simple assay for TMPRSS2:ERG gene fusion detection in prostate cancer urine specimens. Total RNA which potentially include TMPRSS2:ERG transcripts is first Rostad et al. found elevated TMPRSS2:ERG fusion transcripts correlate with high serum PSA, pathological stage, and Gleason score. 36 However, other contradictory studies found the converse. 37, 38 Problems with TMPRSS2 include the lower frequency of the fusion in some populations leading to lower screening sensitivity 39, and the identification

Recurrent chromosomal rearrangements such as fusion genes are associated with cancer initiation and progression. Prostate cancer (PCa) is a leading cause of cancer-related deaths in men and the TMPRSS2-ERG gene fusion is a recurrent biomarker in about 50% of all prostate cancers. However, current TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product.

Abstract Background: Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine.

Through the years, other urinary RNA biomarkers have been evaluated, including the well-known TMPRSS2:ERG transcript, as well as many messenger RNAs, long non coding RNAs and micro-RNA.

In the ongoing search for more specific biomarkers for PCa, prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (ERG, also known as TMPRSS2-ERG) gene fusion transcripts have been identified as promising urinary novel biomarkers [3], [4]. In all patients, the urine samples were collected prior to biopsy or treatment. Polymerase chain reaction with reverse transcription was performed to detect the expression level of PCA3, HOXC6, DLX1 and the presence of the TMPRSS2:ERG transcript. The TMPRSS2:ERG gene fusion (T2:ERG) is found in up to 50% of PCa and results in androgen-dependent overexpression of ERG, which has been demonstrated to be a key regulator of differentiation, apoptosis, embryonic development, cell proliferation, and in flammation (8).

Urine TMPRSS2: ERG Fusion Transcript as a Biomarker for Prostate Cancer: Literature Review. Sanguedolce F, Cormio A, Brunelli M, D’Amuri A, Carrieri G, Bufo P, Cormio L

MPS measures post-digital rectal exam (DRE) urine expression levels of the TMPRSS2:ERG and prostate cancer antigen 3 (PCA3) transcripts, in addition to serum PSA. 2 MPS was endorsed by the National Comprehensive Cancer Network for consideration as a risk stratification tool in men with elevated PSA when deciding upon biopsy.

Such integration is particularly beneficial for detecting low-abundance biomarkers such as miRNAs or TMPRSS2-ERG fusion transcripts, where preconcentration and amplification are often necessary for achieving clinically relevant sensitivity.

Like PCA3, TMRPSS2-ERG transcripts are detectable in the urine, and given sensitivity concerns, multiple studies have attempted to combine TMRPSS2-ERG gene fusions with other biomarkers (includ-ing PCA3) for PCa early detection [2]. In this study, we analyzed the current role of urinary gene fusion transcripts involving v-ets erythroblastosis virus E26 oncogene homolog, commonly known as ERG, and the androgen-regulated gene transmembrane protease, serine 2 (TMPRSS2), as a biomarker for PCa. Used as a single marker, urinary TMPRSS2:ERG has low sensitivity but high specificity. We recently reported the identification of recurrent gene fusions in the majority of prostate cancers involving the 5′ untranslated region of the androgenregulated gene TMPRSS2 and the ETS family members ERG, ETV1, and ETV4. Here we report the

Patient summary Incorporation of two prostate cancer (PCa)-specific biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum prostate-specific antigen (or a multivariate risk calculator) for predicting the presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score, uses models validated in this study and is clinically available to provide

[17] Cornu JN, Cancel-Tassin G, Egrot C, Gaffory C, Haab F, Cussenot O. Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer. Over the last decade and more, many biomarkers have been proposed and tested (HK-2, Pro-PSA, PCA3, TMPRSS2:ERG fusion transcripts, miRNA, just to name a few) but we still await that magical combination of a readily available, reproducible, and hopefully inexpensive biomarker with high sensitivity and specificity.

By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer. While TMPRSS2:erg fusion and PCA3 are both commercially available in the United States (PCA3 from HOLOGIC/Progensa and TMPRSS2:erg fusion may be ordered as part of the MI Prostate Score (MIPS) from the University of Michigan, ongoing work for a series of other biomarkers that may be quantified in the urine are on the way. RT-PCRs were performed with different primer couples to detect the most frequent T2:ERG gene fusion events. To ensure the detection of T2:ERG fusion transcripts involving TMPRSS2 exon 1 and ERG exon 4, a nested PCR was performed by using 1.5 µl of the first PCR amplification, previously diluted 1:5.

TMPRSS2:ERG Fusion Transcript as a Biomarker examination (DRE), urine has become the optimal substrate for noninvasive biomarker testing.12 Current technologies have widened the spectrum of Genetic rearrangement of TMPRSS2 regulatory sequences and coding sequences of the ERG gene has been detected in nearly half of prostate cancers. Quantitative assays to detect such TMPRSS2-ERG gene fusion have been limited to real time PCR techniques There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, Urine TMPRSS2: ERG Fusion Transcript as a Biomarker for Prostate Cancer: Literature Review. Sanguedolce F, Cormio A, Brunelli M, D’Amuri A, Carrieri G, Bufo P, Cormio L Clin Genitourin Cancer, 14 (2):117-121, 17 Dec 2015 TMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the most advanced urine-based prostate cancer (PCa) early detection biomarkers. Validate logistic regression models, termed Mi-Prostate Score (MiPS), that incorporate serum

Incorporation of two prostate cancer (PCa)-specific biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum prostate-specific antigen (or a multivariate risk calculator) for predicting the presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score, uses models