Identification of two distinct regions of allelic imbalance on chromosome 18q in metastatic prostate cancer

Like most cancers, prostate cancer (CAP) is believed to be the result of the accumulation of genetic alterations within cells. Previous studies have implicated numerous chromosomal regions with elevated rates of allelic imbalance (AI), using mostly primary CaPs with an unknown disease outcome. These regions of Al are proposed sites for tumor suppressor genes. One of the regions previously implicated as coding for at least one tumor suppressor gene is the long arm of chromosome 18 (18q). To confirm this observation, as well as to narrow the critical region for this putative tumor suppressor, we analyzed 32 metastatic CaP specimens for Al on chromosome 18q. Thirty-one of these 32 specimens (96.8%) exhibited Al at one or more loci on chromosome 18q. Our analysis using 17 polymorphic markers revealed statistically significant Al on chromosome 18q at 3 markers, D18S35, D18S64 and D18S461. Using these markers as a guide, we have been able to identify 2 distinct minimum regions of Al on 18q. The first region is between the genetic markers D18S1119 and D18S64. The second region lies more distal on the long arm of the chromosome and is between the genetic markers D18S848 and D18S58. To determine if 18q loss is a late event in the progression of CaP, we also examined prostatic intraepithelial neoplasia (PIN) and primary prostate tumors from 17 patients for Al with a subset of 18q markers. We found significantly higher Al in the metastatic samples. Our results are consistent with 18q losses occurring late in CaP progression. (C) 2000 Wiley-Liss, Inc.