Genetic changes in clinically organ-confined prostate cancer by comparative genomic hybridization

• Published in: Urology (Ridgewood, N.J.) N.J.), 2000-11, Vol.56 (5), p.880-885
• Main Authors: Fu, Wenting, Bubendorf, Lukas, Willi, Niels, Moch, Holger, Mihatsch, Michael J, Sauter, Guido, Gasser, Thomas C
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Aberrations - genetics; Chromosomes, Human, Pair 13 - genetics; Chromosomes, Human, Pair 18 - genetics; Chromosomes, Human, Pair 5 - genetics; Chromosomes, Human, Pair 6 - genetics; Chromosomes, Human, Pair 8 - genetics; Disease Progression; DNA Probes; DNA, Neoplasm - analysis; Humans; Male; Medical sciences; Neoplasm Staging; Nephrology. Urinary tract diseases; Prostatectomy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Tumors of the urinary system; Urinary tract. Prostate gland; X Chromosome - genetics
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(00)00722-6

Objectives. The genetic basis underlying prostate cancer development and progression is poorly understood. The primary aim of this study was to identify chromosomal regions important for progression in clinically localized prostate cancer removed by radical prostatectomy. Methods. Comparative genomic hybridization was used for whole genome screening of DNA sequence copy number alterations in 28 pathologically organ-confined tumors (pT2) and 28 tumors with infiltration of the seminal vesicles (pT3b). Results. Comparative genomic hybridization analysis showed on average 2.0 ± 2.4 chromosomal alterations per tumor with more frequent losses (mean 1.3 ± 1.8) than gains (mean 0.7 ± 1.0). The percentage of tumors without alterations was higher in Stage pT2 (21%) than in Stage pT3b (50%). Losses of 8p (21%), 13q (21%), 5q (14%), 16q (14%), and 18q (13%) and gains of Xq (21%) and 8q (9%) were the most prevalent changes. Distinct regional alterations included minimal overlapping regions of loss at 5q13-q21, 6q14-q21, and 18q21-qter. There was only a small increase in the number of alterations from Stage pT2 to Stage pT3b (mean 1.6 ± 2.3 versus 2.5 ± 2.4). However, two individual alterations—gain of 8q and loss of 18q—were significantly more frequent in Stage pT3b than in Stage pT2 prostate cancer ( P = 0.02 and P = 0.04, respectively), suggesting that genes in these regions may be important for prostate cancer progression. Conclusions. The detection of chromosome 8q gains and 18q losses and the identification of the corresponding target genes could become a molecular tool for better characterization of clinically localized prostate cancer.