COMPARATIVE GENOMIC HYBRIDIZATION, ALLELIC IMBALANCE, AND FLUORESCENCE IN-SITU HYBRIDIZATION ON CHROMOSOME-8 IN PROSTATE-CANCER
COMPARATIVE GENOMIC HYBRIDIZATION, ALLELIC IMBALANCE, AND FLUORESCENCE IN-SITU HYBRIDIZATION ON CHROMOSOME-8 IN PROSTATE-CANCER
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DOI：
10.1002/gcc.2870110304
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发表时间：
1994-11-01
影响因子：
3.7
通讯作者：
JENSEN, RH
中科院分区：
文献类型：
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作者：
CHER, ML;MACGROGAN, D;JENSEN, RH
由于原代肿瘤细胞培养的问题，传统的细胞遗传学对前列腺癌染色体改变几乎没有什么有见地的信息。本研究的主要目的是确定比较基因组杂交（CGH）检测和定位前列腺肿瘤基因缺失的能力。第二个目的是将多种检测方法应用于单个肿瘤，作为破译前列腺癌遗传改变机制的一种手段。比较CGH结果与18例标本（17例恶性和1例良性）8号染色体上29个不同位点的等位基因不平衡测量结果。CGH检测没有变化的情况下，所有的信息PCR/RFLP位点被保留，并检测到所有的p臂缺失组成的至少两个位点。我们估计，在这项研究中，CGH检测到的最小缺失约为20-30 cM。亚染色体臂缺失的物理定位CGH与等位基因不平衡定位PCR/RFLP相关良好：8 p上88%的位点和8 q上92%的位点的数据一致。同时对所选标本进行多着丝粒探针荧光原位杂交（FISH）和DNA含量流式细胞术（FCM）。FISH发现2例8号染色体异倍体。在这两个案例和其他三个，CGH显示同时p臂缺失和q臂增益，这表明等染色体8 q的形成。总之，这些数据表明，简单的染色体畸变是负责等位基因损失8 p和等位基因增益8 q在前列腺肿瘤的显着数量。我们还使用CGH来检查整个基因组中的相对DNA序列拷贝数。与8 p丢失相关的变化通常包括8 q的增加和13 q、16 p、16 q、17 p、17 q、20 q和Y的丢失。8便士丢失的病例显示的变化数量是没有8便士丢失的病例的五倍。(C)1994 Wiley-Liss，Inc.
Due to problems with primary tumor cell culture, conventional cytogenetics has yielded little insightful information on chromosomal alterations in prostate cancer. The primary aim of this study was to define the ability of comparative genomic hybridization (CGH) to detect and map genetic deletions in prostate tumors. A secondary aim was to apply multiple assays to individual tumors as a means of deciphering the mechanisms of genetic alterations in prostate cancer. CGH results were compared with allelic imbalance measurements at 29 distinct loci on chromosome 8 in 18 specimens(17 malignant and I benign). CGH detected no changes in cases where all informative PCR/RFLP loci were retained and detected all p arm deletions consisting of at least two loci. We estimate that in this study, the smallest deletions detected by CGH were approximately 20-30 cM. Physical mapping of subchromosomal arm deletions by CGH correlated well with allelic imbalance mapping by PCR/RFLP: The data agreed at 88% of loci on 8p and 92% of loci on 8q. Fluorescence in situ hybridization (FISH) with multiple centromere probes and DNA content flow cytometry (FCM) also was performed on selected specimens. FISH revealed two cases of chromosome 8 aneusomy. In these two cases and three others, CGH showed simultaneous p arm deletion and q arm gain, suggesting isochromosome 8q formation. Together, these data suggested that simple chromosomal aberrations were responsible for allelic losses on 8p and allelic gains on 8q in a significant number of prostate tumors. We also used CGH to examine relative DNA sequence copy number throughout the genome. Changes frequently associated with 8p loss include gains of 8q and losses of 13q, 16p, 16q, 17p, 17q, 20q, and Y. Cases with 8p loss exhibited five times the number of alterations as did cases without 8p loss. (C) 1994 Wiley-Liss, Inc.