Prevalence of TMPRSS2–ERG and SLC45A3–ERG gene fusions in a large prostatectomy cohort

Esgueva, Raquel; Perner, Sven; LaFargue, Christopher J.; Scheble, Veit; Stephan, Carsten; Lein, Michael; Fritzsche, Florian; Dietel, Manfred; Kristiansen, Glen; Rubin, Mark A.

doi:10.1038/modpathol.2009.193

Cited by 134 publications

(127 citation statements)

References 33 publications

(54 reference statements)

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…30 TMPRSS2-ERG gene fusion has been described in 43 to 55% of primary prostate cancers cases. 1,2,[31][32][33] Most studies evaluated clinically localized prostate cancer samples, but did not take into account the zonal subdivision of the prostate gland and the zone of origin of the tumors.…”

Section: Discussionmentioning

confidence: 99%

ERG rearrangement is present in a subset of transition zone prostatic tumors

et al. 2010

Self Cite

View full text Add to dashboard Cite

A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and Z8 in 7 cases. Median tumor volume was 200 mm 2 . TMPRSS2-ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2-ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.

show abstract

Section: Discussionmentioning

confidence: 99%

ERG rearrangement is present in a subset of transition zone prostatic tumors

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…It remains to be established whether the gene fusion plays a role in PIN to cancer progression or can even play a role in earlier stages of prostate cancer development. At a low frequency, ERG overexpression is not caused by fusion to TMPRSS2, but by fusion to SLC45A3 or NDRG1, two other androgen-regulated genes that are preferentially expressed in the prostate (Table 1; Esgueva et al 2010). These two fusion partners do not map to 21q22, indicating that chromosomal proximity is important but not essential for the fusion event.…”

Section: Functions Of Ets Transcription Factorsmentioning

confidence: 99%

ETS fusion genes in prostate cancer

Tandefelt¹,

Boormans²,

Hermans³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostatespecific. 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. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

show abstract

“…Formalin-fixed, paraffin-embedded tissue blocks from radical prostatectomy specimens were used for tissue microarray generation, using the method described previously. 4 Each patient is represented by a total of four tissue cores on the tissue microarray, including three with tumor and one with normal prostate epithelia. Of these 206 patients, analyzable FISH data of TMPRSS2/ERG, AR, and PTEN were generated from 154, 167, and 160 patients, respectively.…”

Section: Patient Samplesmentioning

confidence: 99%

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Jeldres

Glaskova

et al. 2016

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

Multiple biomarkers are needed to distinguish aggressive from indolent prostate cancer. We tested the prognostic utility of a three-marker fluorescent in situ hybridization (FISH) panel (TMPRSS2/ERG rearrangements, AR gain, and PTEN deletion) in a retrospective cohort (n Z 210; median follow-up, 5.7 years). PTEN deletion was associated with an increased risk of biochemical recurrence (BcR; hazard ratio, 3.58; 95% CI, 1.39e9.22; P < 0.01) by multivariable Cox regression analyses and earlier BcR (P < 0.02) by Kaplan-Meier analysis. AR gain coexisted with X-chromosome gain and was associated with advanced tumor stage. When this panel was applied, two categories of combinatorial abnormalities proved clinically important. First, PTEN deletion without TMPRSS2/ERG rearrangement was enriched in pT3/4 tumors (70% versus 48%) and tumors with Gleason grades of 8 to 9 (60% versus 17%) compared with the entire cohort. These patients had earlier BcR than patients with normal FISH panel results (P < 0.01). In contrast, patients with PTEN deletion and ERG rearrangement had a BcR rate similar to patients who tested normal for all three markers (P > 0.1). Second, AR gain and concurrent trisomy 10 without TMPRSS2/ERG rearrangement were enriched in pT3/4 tumors and tumors with Gleason grades of 8 to 9. The three-marker FISH panel demonstrated prognostic utility and identified genomic aberrations associated with advanced disease state and early BcR in prostate cancer. (J Mol Diagn 2016, 18: 215e224; http://dx

show abstract

Prevalence of TMPRSS2–ERG and SLC45A3–ERG gene fusions in a large prostatectomy cohort

Cited by 134 publications

References 33 publications

ERG rearrangement is present in a subset of transition zone prostatic tumors

ERG rearrangement is present in a subset of transition zone prostatic tumors

ETS fusion genes in prostate cancer

Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence

Contact Info

Product

Resources

About