Detection of novel amplification units in prostate cancer

Genome-wide screening for regions of genetic gains and losses on nine prostate cancer cell lines (PC3, DU145, LNCaP, CWR22, and derived sublines) was carried out using comparative genomic hybridization on a 35 K longmer oligonucleotide microarray (arrayCGH). Compared to conventional chromosomal CGH more deletions and small regions of gains, particularly in pericentromeric regions and regions next to the telomers, were detected. As a proof for the high-resolution of arrayCGH we further analyzed a small amplification unit of 1.7 MB at 9p13.3, which was found in CWR22 and CWR22-Rv1. Increased copy number was confirmed by fluorescence in situ hybridization using the BAC clone RP11-165H19 from the amplified region comprising the two genes interleukin 11 receptor alpha (IL11-RA) and dynactin 3 (DCTN3). Using quantitative real time PCR (qPCR) we could demonstrate that IL11-RA is the gene with the highest copy number gain in the cell lines compared to DCTN3 suggesting IL11-RA to be the amplification target. Screening of 20 primary prostate carcinomas by qPCR revealed a high frequency of IL11-RA copy number gain in 75% of the tumors analyzed. Gain of DCTN3 was only found in two cases together with a gain of IL11-RA. Thus, IL11-RA is a frequently amplified gene in prostate cancer with amplification being supposed to be one mechanism of IL11-RA overexpression in this tumor type. Keywords: comparative genomic hybridization whole genome array comparative genomic hybridization