Comparative genomic hybridization reveals DNA copy number gains to frequently occur in human prostate cancer

Abstract

BACKGROUND Despite intensive studies over many years, there is only limited knowledge on the genetic changes underlying the development and progression of prostate cancer. No specific prostate carcinoma‐related genetic event has yet been identified. METHODS In order to gain an overall view of regional chromosome gains and losses, comparative genomic hybridization (CGH) was used on a series of 16 prostate adenocarcinomas. Five benign prostate hyperplasia (BPH) samples were also evaluated. RESULTS Using CGH, chromosome alterations were observed in 81% of the prostate carcinomas analyzed. Gains of DNA copy numbers were found as the predominant imbalance, with chromosomes 3q (56%), 12q (56%), 8q (50%), Xq (50%), 4 (44%), 6q (44%), 5 (38%), 7q (38%), 9p (38%), and 13q (31%) being most frequently involved. Whereas DNA copy number gains comprised the whole chromosome or almost a whole arm of chromosomes 4, 5, 6, 9, and 13, the minimal overlapping regions on the other chromosomes were mapped to 3q25–q26, 8q21–q22, 12q13–q21, 7q31, and Xq22–q25. High‐level amplifications were not found. Other chromosomes with nonrandom gains or losses of DNA sequences were discovered. The five BPH samples were found to be normal. CONCLUSIONS Amplification events at different chromosomal sites seem important in prostate cancer development. A new chromosome region with DNA copy number gains was identified on 12q, while other regions on 3q, 7q, 8q, and Xq were confirmed or narrowed down, indicating a possible role of known or putative protooncogenes in these regions for prostate cancer growth. Our low detection rate of DNA losses may to some part be explained by CGH immanent technical limitations. Prostate 39:79–86, 1999. © 1999 Wiley‐Liss, Inc.

Chromosomal changes during development and progression of prostate adenocarcinomas

“…Frequently occurring gains of whole chromosomes 16, 17 and 20 reflect the aneuploid karyotype of the tumours. The frequent finding of gain on chromosome 12q is in good agreement with a recent publication (Sattler et al, 1999) reporting on frequent copy number gains in human prostate cancer. Losses on 8p and 6q as well as gains on 8q and of chromosome 7, which were considered to be typical aberrations for prostate cancer (for review see Bova and Isaacs, 1996), were also detected in primary tumours investigated in this study, but at a lower frequency.…”

Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder

“…This chromosome location has been identi®ed by loss of heterozygosity studies as a site of a putative tumor suppressor gene or genes for breast carcinoma, colon carcinoma, neuroblastoma, non small cell lung carcinoma, melanoma, hepatocellular carcinoma, prostate, pancreatic endocrine tumors and Wilms' tumors (Nagai et al, 1995;Praml et al, 1995;Bieche et al, 1998;Martinsson et al, 1997;Ebrahimi et al, 1999;Gasparian et al, 1998;Chen et al, 1996;Boni et al, 1998;Williamson et al, 1997;Steenman et al, 1997;Sattler et al, 1999). However, we have not been unable to detect a mutation in the two TERE1 exons in 30 TCCs/matched normal PBLs except in the RT4 bladder tumor cell line.…”

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

“…To reveal the most abundant chromosomal imbalances detected in prostate carcinoma, we performed an exhaustive search of six CGH studies, including a total of 145 primary prostate cancers (Sattler et al, 1999;Alers et al, 2001;Verdorfer et al, 2001;Zitzelsberger et al, 2001;Steiner et al, 2002;Wolter et al, 2002;Paris et al, 2003) as well as one array CGH study of 16 primary prostate cancers (Paris et al, 2003). In order to identify candidate genes that may be directly affected by these chromosomal imbalances, we screened a list of the top 250 most up-regulated and down-regulated genes as revealed by a recent meta-analysis of four independent expression microarrays including 61 prostate cancer samples (Rhodes et al, 2002).…”

“…First, an exhaustive search for imbalanced chromosomal regions from seven CGH and array CGH studies was performed (Sattler et al, 1999;Alers et al, 2001;Verdorfer et al, 2001;Zitzelsberger et al, 2001;Steiner et al, 2002;Wolter et al, 2002;Paris et al, 2003). Next, the results were compared to a recent meta-analysis of four independent expression array data sets (Rhodes et al, 2002) in order to define candidate genes located within regions recurrently changed in copy number.…”