Molecular Pathways Associated with ERG Rearranged PTEN Deleted Hormone Refractory Prostate Cancer
M Alshalalfa, A Bakkar, K Sircar, JA Squire, R Alhajj, TA Bismar. University of Calgary, Calgary, AB, Canada; University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada; MD Anderson Cancer Center, Houston, TX; Queens University and Kingston Hospital, Kingston, ON, Canada
Background: ERG rearrangements and PTEN deletions have been proposed to signify specific molecular subtype of prostate cancer (PCA) associated with worse prognosis compared to tumors with none of those genetic aberrations. Here, we investigated gene expression differences between those two classes of tumors to identify potential pathways and genetic targets.
Design: 6144 informative genes from 59 HRPCA samples were previously interrogated using the DASL platform. We used Singular Value Decomposition (SVD) which has recently been explored as an effective method for analyzing gene expression data to reanalyze those genes based on their ERG and PTEN status (assessed by FISH). SVD based approach is attractive because it provides a mathematical framework for processing and modeling genome-wide expression data and considers all genes to assess the significance of each individual gene, unlike other methods. Thus using SVD as a selection model makes our study more comprehensive and robust with less false discovery rate.
Results: SVD identified a group of 16 differentially expressed genes between the two groups (n=11). Genes associated with cell adhesion and cell motility pathways (MCAM and ADAM9) as well as several tumor suppressor genes, like CHD5 and SPINT2, were among the most significant deregulated genes between the two groups with the first three showed to be down regulated in the ERG rearranged/PTEN deleted tumors. Other genes, related to apoptosis (SDCBP), chromatin remodeling (CHD5) as genes related to NF-kappaB were among the top discovered genes. Other identified genes (like Syntenin, POLD1, Sec61B, TCEAL4, HINT1) have poorly characterized role in cancer in general and PCA in particular.
Conclusions: ERG rearranged/PTEN deleted tumors represent distinct subclass of PCA associated with downregulation of genes related to cell adhesion, cell motility as well as several tumor suppressor genes. As this represent a distinct subclass of tumors, investigating the genes identified here could lead to better understanding of the molecular mechanisms of this subclass of tumors. Further characterization and targeting of those discovered genes/pathways maybe beneficial in counteracting disease progression in this subclass of PCA.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 8:30 AM
Platform Session: Section A, Tuesday Morning