Diversity of TMPRSS2-ERG fusion transcripts in the human prostate

Clark, Jeremy; Merson, Sue; Jhavar, Sameer; Flohr, Penelope; Edwards, Sandra E.; Foster, Christopher S.; Eeles, Rosalind; Martin, Francis L.; Phillips, David H.; Crundwell, Malcolm; Christmas, T. J.; Thompson, Alan; Fisher, Cyril; Kovács, Gyula; Cooper, Christopher S.

doi:10.1038/sj.onc.1210070

Cited by 222 publications

(242 citation statements)

References 12 publications

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“…Several studies have consistently confirmed that fusion at exon 1 of TMPRSS2 is the most common variant (Tu et al, 1996;Wang et al, 2006;Clark et al, 2007). However, Clark et al (2007) also found that distinct patterns of hybrid transcripts from separate areas of the same tumour which would make associations of clinical significance more difficult. These and other separate fusion transcripts will require further study to examine for their association with prostate cancer prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Many other rare transcripts of this gene fusion have been described (Soller et al, 2006;Wang et al, 2006;Clark et al, 2007;Liu et al, 2007;Tu et al, 2007). We only examined the most common fusions of TMPRSS2 exon 1 with exon 4 of ERG transcript.…”

Section: Discussionmentioning

confidence: 99%

“…Alternative fusions are possible, but having two or more distinct translocations on each allele in a single tumour area is not likely rather, these transcripts may arise from alternative splicing of the fused exons, after transcription. Alternative splicing of ERG gene is well studied, with up to 17 variants being described (Soller et al, 2006;Clark et al, 2007). Several studies have consistently confirmed that fusion at exon 1 of TMPRSS2 is the most common variant (Tu et al, 1996;Wang et al, 2006;Clark et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Alternative splicing of ERG gene is well studied, with up to 17 variants being described (Soller et al, 2006;Clark et al, 2007). Several studies have consistently confirmed that fusion at exon 1 of TMPRSS2 is the most common variant (Tu et al, 1996;Wang et al, 2006;Clark et al, 2007). However, Clark et al (2007) also found that distinct patterns of hybrid transcripts from separate areas of the same tumour which would make associations of clinical significance more difficult.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…10,11 In prostate cancer, multiple TMPRSS2-ERG fusion variants have been identified at the transcript level, most of them involving only the 5 0 untranslated sequence of TMPRSS2. 6,[12][13][14][15] The TMPRSS2-ETS fusions thus lead to overexpression of the ERG or ETV protein induced by the TMPRSS2 promoter. In contrast to other translocations involving the ERG gene, for example, EWS-ERG fusion, no fusion protein is expected in most TMPRSS2-ERG fusions.…”

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confidence: 99%

Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues

et al. 2007

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Recurrent gene fusions between TMPRSS2 and ETS family genes have recently been shown to occur at a high frequency in prostate cancer. In this study, we used formalin-fixed paraffin-embedded tissue and evaluated both TMPRSS2-ERG and TMPRSS2-ETV1 fusions by reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). The results were correlated to overexpression of the downstream ERG and ETV1 sequences. Of 82 cases examined, TMPRSS2-ETV1 fusion was seen in only one case, by FISH. In comparison, TMPRSS2-ERG fusion was documented in 35 cases (43%) by either RT-PCR or FISH. Deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion (81 vs 19%). RT-PCR and FISH results correlated well, with most positive cases resulting in overexpression of downstream ERG sequences. Several TMPRSS2-ERG fusion transcript variants were identified, most of which are predicted to encode truncated ERG proteins. Prostate cancer of Gleason's scores 6 or 7 had more frequent TMPRSS2-ERG fusions than higher-grade tumors, but this difference was not statistically significant (P ¼ 0.42). On the other hand, mucin-positive carcinomas more often harbor such gene fusions when compared to mucin-negative tumors (P ¼ 0.004). These morphological correlates, and more importantly the potential correlation of such fusions to clinical outcome and treatment responses, should be further explored. Modern Pathology (2007) 20, 921-928;

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Fusion sequencing via terminator‐assisted synthesis (FTAS‐seq) identifies TMPRSS2 fusion partners in prostate cancer

et al. 2023

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Genetic rearrangements that fuse an androgen‐regulated promoter area with a protein‐coding portion of an originally androgen‐unaffected gene are frequent in prostate cancer, with the fusion between transmembrane serine protease 2 (TMPRSS2) and ETS transcription factor ERG (ERG) (TMPRSS2‐ERG fusion) being the most prevalent. Conventional hybridization‐ or amplification‐based methods can test for the presence of expected gene fusions, but the exploratory analysis of currently unknown fusion partners is often cost‐prohibitive. Here, we developed an innovative next‐generation sequencing (NGS)‐based approach for gene fusion analysis termed fusion sequencing via terminator‐assisted synthesis (FTAS‐seq). FTAS‐seq can be used to enrich the gene of interest while simultaneously profiling the whole spectrum of its 3′‐terminal fusion partners. Using this novel semi‐targeted RNA‐sequencing technique, we were able to identify 11 previously uncharacterized TMPRSS2 fusion partners and capture a range of TMPRSS2‐ERG isoforms. We tested the performance of FTAS‐seq with well‐characterized prostate cancer cell lines and utilized the technique for the analysis of patient RNA samples. FTAS‐seq chemistry combined with appropriate primer panels holds great potential as a tool for biomarker discovery that can support the development of personalized cancer therapies.

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Diversity of TMPRSS2-ERG fusion transcripts in the human prostate

Cited by 222 publications

References 12 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

Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues

Fusion sequencing via terminator‐assisted synthesis (FTAS‐seq) identifies TMPRSS2 fusion partners in prostate cancer

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