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T2-Erg Team Project

376
Sanda, MartinEmory University

No involved investigator sites defined.

T2-erg, PCA3
Genomics
Prostate and Urologic Cancers Research Group
2

Prostate cancer (PCa) is the third leading cause of cancer-related deaths among United States men, accounting for 33% of such diagnosed cancers.(1) An estimated 186,320 new cases of PCa were diagnosed in 2006, with an associated mortality rate of 28,660.(15,16) Unfortunately the currently used screening tools, PSA and related tests, have limited ability to detect PCa. In fact, the Prostate Cancer Prevention Trial detected PCa in 6.6%, 10.1%, 17%, 23.9% and 26.9% of subjects with “normal” PSA values of <0.5, 0.6-1.0, 1.1-2.0, 2.1-3.0 and 3.1-4.0 ng/ml respectively. Since the majority of men between the ages of 45 and 75 had PSA values of <4.0 ng/ml, it has been suggested that 15% of high-grade cancer cases, were missed due by PSA-only evaluation.(30,33) The EDRN PCA3 validation study has demonstrated the value of PCA3 in the early detection of prostate cancer . An important aspect of that project was the development of a large prospective blood and urine biospecimen repository suitable for other biomarker studies. In a series of studies led by Arul Chinnaiyan, the BDL at University of Michigan showed that gene rearrangements that result in the prostate-specific promoter region of T2:ERG being juxtaposed adjacent to sequences encoding functional regions of erg or other ets transcription factors are a common gene rearrangement present in more than half of prostate cancers. Other groups subsequently verified that the T2:erg rearrangement is commonplace in prostate cancer tissue. Subsequently, the Chinnaiyan BDL collaborating with the Harvard-Michigan-Cornell CVC found that: a) T2:ERG gene fusion is detected by FISH at biopsy in 46% of prostate cancers; b) presence of T2:erg fusion in biopsy tissue in a Swedish cohort of prostate cancer patients who were managed conservatively was associated with significantly greater rates of lethal progression; c) T2:ERG gene fusion can be detected in post-DRE urines, d) Multiplex models combining T2:ERG fusion urine assay with serum PSA, and urine PCA3, can effectively predict presence of prostate cancer on biopsy and improves upon using PSA alone. Recently, a multicenter prevalidation study has recently found that T2:erg has the ability to distinguish clinically significant prostate cancer in both biopsy and radical prostatectomy cohorts (see Preliminary Data below). Moreover, new discoveries are moving along the prevalidation pathway and may soon become available for further validation by the EDRN. The availability of a carefully annotated tissue bank with urinary and serum specimen resources provide for these future biomarkers including, but are not limited to, ETV1, PCAT-1, PCAT-14, SChLAP1, DNA methylation markers to be tested (WFDC2, MAGI2, MEIS2, AOX1, NTN4, C9orf125, AMT and S100A16, along with GSTP1), other non coding RNAs, SPOP, and SPINK (Chinnaiyan).

Primary Specific Aims Aim 1:   To validate the performance of urinary T2:erg in a multiplex model in combination with PCA3 predicting the diagnosis of histologically clinically significant prostate cancer among men without prior evidence of prostate cancer Secondary Aims Aim 1:   To evaluate the sensitivity, specificity, PPV, NPV and absolute risk prediction by T2:erg/PCA3 combined and multiplexed with other biomarkers and clinical variables in the detection of histologically clinically significant prostate cancer Aim 2:    To validate the performance of urinary T2:erg in a multiplex model in combination with PCA3 predicting the diagnosis of ANY prostate cancer Aim 3:    To investigate whether the multiplex model performance is improved by addition of % free PSA, PSAV, -2proPSA, and other markers in development Aim 4:   To evaluate the correlation between urinary and tissue based T2:erg and prostate biopsy tumor grade
Transcription mediated amplification based assay

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.


Announcement 09/14/2014

Thank you to everyone who helped make the 9th EDRN Scientific Workshop a success. We look forward to seeing everyone at the 28th EDRN Steering Committee Meeting from March 31-April 2, 2015, in Atlanta, GA.

Announcement 06/05/2014


Funding Opportunity Available

Both RFAs for Molecular and Cellular Characterization of Screen-Detected Lesions have been published.

RFA-CA-14-010.html

and

RFA-CA-14-011.html