Array 比较基因组杂交鉴定胆管癌中的新潜在治疗靶点。
Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma.
机构信息
Department of Hepatopancreaticobiliary Surgery, Imperial College London, London, UK.
出版信息
HPB (Oxford). 2011 May;13(5):309-19. doi: 10.1111/j.1477-2574.2010.00286.x. Epub 2011 Mar 10.
BACKGROUND
Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets.
METHODS
DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment.
RESULTS
DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained.
CONCLUSIONS
We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.
背景
胆管癌（CC）是一种罕见的肿瘤，预后较差。由于传统的医学治疗方法提供的生存获益有限，目前手术是唯一可能治愈的方法。我们评估了 CC 中的 DNA 拷贝数（CN）改变，以确定新的治疗靶点。
方法
从 32 个 CC 样本中提取 DNA。使用包含 3400 个 BAC 克隆的微阵列载玻片进行细菌人工染色体（BAC）阵列比较基因组杂交，这些 BAC 克隆覆盖整个人类基因组，距离为 1 Mb。在 R 统计环境中分析数据。
结果
DNA CN 增益（89 个区域）比 DNA CN 损失（55 个区域）更频繁。在所有病例中，16、17、19 和 22 号染色体上都发现了 6 个增益区域。在 1、5、7、9、11、12、16、17、19、20 和 21 号染色体上，20 个区域经常被增益。覆盖 ERBB2、MEK2 和 PDGFB 基因的 BAC 克隆在所有病例中都被增益。覆盖 MTOR、VEGFR3、PDGFA、RAF1、VEGFA 和 EGFR 基因的区域经常被增益。
结论
我们鉴定出 11 个有用的分子靶标区域的 CN 增益。本研究和其他研究中发现某些区域存在可变增益，支持在治疗前对 CC 进行分子分层，以便根据个体患者的情况进行治疗定制。
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