Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression

Nam, Robert K.; Sugar, Linda; Wang, Zhenghui; Yang, Wenyi; Kitching, Richard; Klotz, Laurence; Venkateswaran, Vasundara; Narod, Steven A.; Seth, Arun

doi:10.4161/cbt.6.1.3489

Cited by 148 publications

(128 citation statements)

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“…The presence of the TMPRSS2:ERG fusion gene was established using RT -PCR for all 165 prostate cancer patient samples, described elsewhere (Nam et al, 2007). Briefly, 1 mg of total RNA was reverse transcribed into cDNA using QuantiTect Reverse Transcription Kit (Qiagen Inc., Valencia, CA, USA) in the presence of random and oligo-dT primers.…”

Section: Rt -Pcr and Direct Dna Sequencingmentioning

confidence: 99%

“…All reactions were performed with both the forward and reverse primer sets (F-TAGGCGC GAGCTAAGCAGGAG, R-GTAGGCACACTCAAACAACGACTGG) that yields a 125-bp and (F-CAGGAGGCGGAGGCGGA, R-GGCGGTTGTAGCTGGGGGTGAG) that yields a 595-bp product as described by Tomlins et al (2005). PCR amplified products were resolved by electrophoresis on a 2% agarose gels and bands were excised, purified and sequenced using the ABI 3700 (Applied Biosystems, Foster City, CA, USA) automated DNA sequencer ( Figure 1) (Nam et al, 2007).…”

Section: Rt -Pcr and Direct Dna Sequencingmentioning

confidence: 99%

“…However, because the follow-up period was short (mean 12 months) and the sample size was small (n ¼ 26), we could not determine if this effect was independent of other factors, such as grade, stage and PSA level. We also examined the significance of ETV1 fusion, but did not find any association with cancer recurrence (Nam et al, 2007).…”

mentioning

confidence: 98%

“…Several studies have compared clinicopathological parameters (Perner et al, 2006;Wang et al, 2006;Lapointe et al, 2007;Rajput et al, 2007;Tu et al, 2007) and prognostic significance (Wang et al, 2006;Attard et al, 2007;Demichelis et al, 2007;Lapointe et al, 2007;Nam et al, 2007) of this gene fusion with conflicting results. Two of these studies showed no correlation between histologic grade (Gleason score) (Lapointe et al, 2007;Tu et al, 2007), while others found positive associations (Attard et al, 2007;Rajput et al, 2007).…”

mentioning

confidence: 99%

“…Patients managed and selected for watchful waiting from these cohorts have different baseline distributions in grade, stage and PSA level to patients treated with surgery and may not be comparable. From a small cohort of 26 patients who underwent surgery for clinically localised disease, we recently showed that those with the fusion expression had a significantly higher rate of recurrence compared to patients who lacked the fusion expression (5-year recurrence rate 79.5 vs 37.5%, P ¼ 0.009) (Nam et al, 2007). However, because the follow-up period was short (mean 12 months) and the sample size was small (n ¼ 26), we could not determine if this effect was independent of other factors, such as grade, stage and PSA level.…”

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confidence: 99%

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Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

et al. 2007

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The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT -PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, Po0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI ¼ 3.6 -20.6, Po0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

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Section: Rt -Pcr and Direct Dna Sequencingmentioning

confidence: 99%

Section: Rt -Pcr and Direct Dna Sequencingmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

et al. 2007

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Prostate Cancer

Nelson¹,

Haffner²,

Yegnasubramanian³

2015

Targeted Therapy in Translational Cancer Research

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Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers

et al. 2012

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We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.

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Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression

Cited by 148 publications

References 14 publications

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

Prostate Cancer

Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers

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