Van Den Berg C, Guan X Y, Von Hoff D, Jenkins R, Griffin C, Kallioniemi O, Herath J
University of Texas Health Science Center, San Antonio, Texas 78284, USA.
Clin Cancer Res. 1995 Jan;1(1):11-8.
The primary aim of this report was to examine the significance of increased DNA sequence copy number (gene amplification) in human prostate cancers. Three methodologies (chromosome microdissection, comparative genomic hybridization, and fluorescence in situ hybridization) were combined to (a) identify a common region of gene amplification in human prostate cells and (b) evaluate in patient samples the prevalence of this genetic change in both primary and recurrent prostate samples. The results of chromosome microdissection revealed a common amplified band region (8q24.1-24. 2) in two prostate cases with cytological evidence of gene amplification (double minutes). Fluorescence in situ hybridization using the 8q microdissection probe was performed on fresh tumor touch preparations from 44 randomly selected prostatectomy specimens. Amplification of DNA sequences from 8q24 was observed in 4 (9%) of 44 cases. Four of the 44 patients in this series presented with a positive lymph node at initial diagnosis and 3 of these 4 patients showed 8q amplification. Because of this finding, comparative genomic hybridization and fluorescence in situ hybridization were performed on tumor cells from nine prostate cancer patients with recurrent disease. In eight of nine cases a gain of DNA sequences encompassing 8q24 was observed. Taken together with other evidence implicating 8q gain in prostate cancer progression, these results suggest that the analysis of this genetic change may have diagnostic utility as a marker of prostate cancer progression.
本报告的主要目的是研究人类前列腺癌中DNA序列拷贝数增加(基因扩增)的意义。我们结合了三种方法(染色体显微切割、比较基因组杂交和荧光原位杂交)来:(a)确定人类前列腺细胞中基因扩增的共同区域;(b)评估在患者样本中,这种基因变化在原发性和复发性前列腺样本中的发生率。染色体显微切割结果显示,在两例有基因扩增细胞学证据(双微体)的前列腺病例中,存在一个共同的扩增条带区域(8q24.1 - 24.2)。使用8q显微切割探针进行荧光原位杂交,对44例随机选取的前列腺切除标本的新鲜肿瘤触摸涂片进行检测。在44例病例中有4例(9%)观察到8q24的DNA序列扩增。该系列中的44例患者中有4例在初诊时出现阳性淋巴结,其中3例显示8q扩增。基于这一发现,我们对9例复发性前列腺癌患者的肿瘤细胞进行了比较基因组杂交和荧光原位杂交。在9例病例中有8例观察到包含8q24的DNA序列增加。结合其他暗示8q增加与前列腺癌进展相关的证据,这些结果表明,对这种基因变化的分析可能作为前列腺癌进展的标志物具有诊断价值。