Genomic Biomarkers For Risk Stratification In Prostate Cancer

Editor's Choice
Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Genetics;  Cancer / Oncology
Article Date: 02 Nov 2008 - 0:00 PDT

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MONTEREY, CA, USA (UroToday.com) - In his State-of-the-Art talk, Colin Collins discussed biomarkers for prostate cancer (CaP) risk stratification. He asked where genome copy number profiles can predict CaP recurrences. To explore this, his group used array comparative genomic hybridization (CGH) to identify genes mutations.

The array data displays gene amplification and losses as topographical data. They identified the MEM1 gene as predictive of recurrence after radical prostatectomy. MEM1 is an oncogene, and its upregulation influences metastatic potential. Next, they compared the primary to metastatic tumors to look for differences. There were 64 topographic changes in the primary tumors, but in metastatic lesions there were many more and these were present in up to 80% of lesions. Different mutations appeared in lesions from different metastatic sites. They called the alterations that increased from primary to metastatic tumors "genomic evaluators of metastatic CaP" (GEMCaP).

Several of the GEMCaP identified genes were consistent with known genetic alterations in metastatic CaP. They then incorporated the GEMCaP genes into nomograms and obtained positive predictive value of greater than 75%. The goal is to put together GEMCaP signatures that rival clinical nomograms that include standard pathologic and clinical data. In a gene expression study, 5 GEMCaP genes predicted node status with 95% sensitivity and 80% specificity.

Colin Collins looked at genotypes of TMPRSS2-ERG+/- gene fusions for incorporation into his model to improve the accuracy of predicting progression. In comparing across tumor types, there are many biomarker similarities from CaP to other cancers. This suggests that work in this field many be applicable across tumor types. A potential limitation of this approach includes tumor heterogeneity within a prostate - but still their work suggests that genome profiling of multiple tumors, within the same prostate, has 80-95% genomic concordance. He also showed a new technique (MIP) of using paraffin embedded prostate biopsy tissue to do whole genome arrays and to identify chromosomal aberrations.

He concluded that next generation sequencing will impact our knowledge about tumor behavior and have direct translational potential.

Presented by Colin Collins, MD, at the 84th Annual Meeting of the AUA - Western Section - October 26 - 30, 2008 - Monterey, California

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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