High-resolution array comparative genomic hybridization of chromosome arm 8q:: Evaluation of genetic progression markers for prostate cancer
High-resolution array comparative genomic hybridization of chromosome arm 8q:: Evaluation of genetic progression markers for prostate cancer
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DOI：
10.1002/gcc.20259
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发表时间：
2005-12-01
影响因子：
3.7
通讯作者：
van Dekken, H
中科院分区：
文献类型：
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作者：
van Duin, M;van Marion, R;van Dekken, H
先前已有研究表明，8q拷贝数增加与前列腺癌患者较差的临床预后和肿瘤复发有关。在这项研究中，对原发和转移性前列腺腺癌（n = 22）、前列腺癌异种移植物（n = 9）和细胞系（n = 3）进行了详细的8q基因组分析。我们使用由702个8q特异性BAC克隆组成的全染色体臂序列阵列进行了阵列比较基因组杂交（aCGH）。在染色体带8q21.13 （81-82 Mb）、8q22.1 （94-96 Mb）、8q22. 3 -3 （101-103 Mb）、8q24.13 （124-126 Mb）和8q24.21 （127-129 Mb）处发现了5个拷贝数频繁增加的区域，这是包含MYC癌基因的最末端区域。选择MYC和其他4个区域的13个被认为与癌症相关的基因。通过前列腺癌异种移植PC339的8q aCGH分析检测到的高水平扩增获得了另外两个基因。对这16个基因在26个前列腺标本中进行了定量RT-PCR，包括正常组织（n = 5）、新鲜冷冻腺癌（n = 7）、癌症异种移植（n = 9）和癌细胞系材料（n = 2）。与正常前列腺组织相比，16个基因中有3个在癌症中显著过表达，即PDP位于8q22.1 (95 Mb)， PABPCI位于8q22.3 (102 Mb)， KIAA0196位于8q24.13 （126 Mb）。这些基因可以被认为是前列腺癌的推定进展标记。(c) 2005 Wiley-Liss, Inc。
Copy number increase of 8q has previously been shown to be associated with a poor clinical outcome and tumor recurrence in patients with prostate cancer. In this study, a detailed genomic analysis of 8q was performed of archival primary and metastatic prostatic adenocarcinomas (n = 22), and prostate cancer xenografts (n = 9), and cell lines (n = 3). We performed array comparative genomic hybridization (aCGH) using a whole chromosome arm contig array consisting of 702 8q-specific BAC clones. Five regions of frequent copy number increase were identified, i.e. at chromosome bands 8q21.13 (81-82 Mb), 8q22.1 (94-96 Mb), 8q22.2-3 (101-103 Mb), 8q24.13 (124-126 Mb), and 8q24.21 (127-129 Mb), the most distal region containing the MYC oncogene. MYC and 13 genes of the other four regions with putative relevance to cancer were selected. Two additional genes were derived from high-level amplifications detected by 8q aCGH analysis of prostate cancer xenograft PC339. Quantitative RT-PCR of these 16 genes was performed in a series of 26 prostate specimens, including normal tissue (n = 5), fresh-frozen adenocarcinoma (n = 7), cancer xenograft (n = 9), and cancer cell line material (n = 2). Three of the 16 genes were significantly overexpressed in cancer compared with that in normal prostate tissue, i.e. PDP, located at 8q22.1 (95 Mb), PABPCI located at 8q22.3 (102 Mb), and KIAA0196 located at 8q24.13 (126 Mb). These genes can be considered putative progression markers for prostate cancer. (c) 2005 Wiley-Liss, Inc.