Gene Expression Profiles of Classical and Spermatocytic Seminoma
RK Jain, MA Thorat, R Mehta, Y Polar, A Morimiya, C Sweeney, S Beck, TM Ulbright, S Badve. Indiana University, Indianapolis, IN
Background: Seminomas of the testis occur in two forms: classic seminomas (CS), which give rise to local and distant metastases, and the rare Spermatocytic seminomas (SS), which are virtually benign. SS occur in older patients and have been described only in the testis. The presence of intratubular germ cell neoplasia, histological features of the tumor and immunostains are used to distinguish them. However, the biologic processes that determine the different natural histories have not been well studied, partly due to the rarity of SS. We conducted gene expression profiling using cDNA microarrays to understand these processes with a view of developing targeted therapeutics.
Design: RNA was extracted from SS (n= 8) and CS (n=14) cases using High Pure™ RNA Paraffin Kit (Roche®). cDNA Annealation Selection and Ligation (DASL™) assay was performed with the Sentrix Universal Array (Illumina®) of 502 cancer related genes. Hierarchical clustering and singular value decomposition methods were applied to detect the outliers for quality control purposes. All statistical analyses and clustering were performed using BeadStudio v3.0 (Illumina®).
Results: In unsupervised cluster analysis 2 distinct clusters were noted. CS cases clustered together but separately from the cluster of SS cases. The gene expression profiling reveals 24 up-regulated and 8 down-regulated genes in CS using a stringent cutoff value (p < 0.001). The up-regulated genes include KIT and a number of genes related to DNA transcription and cell proliferation, apoptosis and cell cycle control. Amongst the chemotaxis- and immune-related genes ETS1 and CXCL9 were over-expressed in CS.
Conclusions: Gene expression analysis demonstrates that CS is biologically distinct from SS. The major pathways that are differentially expressed were related to cell proliferation and apoptosis as well DNA transcription. Following further validation, these pathways could serve as targets for therapeutics.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:15 AM
Platform Session: Section A, Monday Morning