Mapping and Gene Expression Profile of the Minimally Overrepresented 8q24 Region in Prostate Cancer

Abstract

We have recently reported that overrepresentation of 8q24 (c-myc) is associated with clinical progression in prostate cancer. In this study, we map the boundaries of the overrepresented region within 8q23-q24 using interphase fluorescent in situ hybridization analysis of paraffin-embedded prostate cancer specimens. One hundred primary prostate cancers and three prostate cancer cell lines were evaluated, and the minimally overrepresented region could be narrowed to the approximately 8.2-Mb region between D8S514 and H47317. This region includes c-myc and is wholly within 8q24. Eukaryotic translation initiation factor 3 subunit 3 does not seem to be overrepresented independent of c-myc in prostate cancer. The cell lines PC3 and DU145 have and do not have 8q24 overrepresentation, respectively. We then selected 39 expressed sequence tags (ESTs) within and surrounding the minimally overrepresented region and performed expression analysis using Northern blot hybridization. Five ESTs/genes including c-myc were overexpressed in both the PC3 cell line and DU145, but the PC3 to DU145 expression ratios were <2. Seven ESTs were overexpressed twofold or more in PC3 compared to DU145. This group included hyaluronan synthase 2, nephroblastoma-overexpressed gene, eukaryotic translation initiation factor 3 subunit 3, and an EST (R69368) encoding a hypothetical protein (BM009). These seven genes as well as c-myc are candidate target genes within the overrepresented 8q24 region and their overexpression may be associated with prostate cancer progression.