Fu W, Bubendorf L, Willi N, Moch H, Mihatsch M J, Sauter G, Gasser T C
Urologic Clinics, University of Basel, Basel, Switzerland.
Urology. 2000 Nov 1;56(5):880-5. doi: 10.1016/s0090-4295(00)00722-6.
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.
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).
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.
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.
前列腺癌发生和进展的遗传基础仍知之甚少。本研究的主要目的是确定在根治性前列腺切除术中切除的临床局限性前列腺癌进展中重要的染色体区域。
采用比较基因组杂交技术对28例病理上器官局限型肿瘤（pT2）和28例精囊浸润型肿瘤（pT3b）的DNA序列拷贝数改变进行全基因组筛选。
比较基因组杂交分析显示，每个肿瘤平均有2.0±2.4个染色体改变，缺失（平均1.3±1.8）比增加（平均0.7±1.0）更常见。pT2期无改变的肿瘤百分比（21%）高于pT3b期（50%）。8p（21%）、13q（21%）、5q（14%）、16q（14%）和18q（13%）的缺失以及Xq（21%）和8q（9%）的增加是最常见的变化。不同的区域改变包括5q13-q21、6q14-q21和18q21-qter处缺失的最小重叠区域。从pT2期到pT3b期，改变的数量仅略有增加（平均1.6±2.3对2.5±2.4）。然而，两个个体改变——8q增加和18q缺失——在pT3b期前列腺癌中比在pT2期更频繁（分别为P = 0.02和P = 0.04），表明这些区域的基因可能对前列腺癌进展很重要。
检测8q增加和18q缺失以及鉴定相应的靶基因可能成为更好地表征临床局限性前列腺癌的分子工具。
