Zhu Hong, Wong Maria Pik, Tin Vicky
Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Department of Pathology, The University of Hong Kong, Hong Kong, SAR, P.R. China.
Int J Oncol. 2014 Jun;44(6):2068-76. doi: 10.3892/ijo.2014.2384. Epub 2014 Apr 11.
Genomic abnormalities are the hallmark of cancers and may harbor potential candidate genes important for cancer development and progression. We performed array comparative genomic hybridization (array CGH) on 36 cases of primary lung adenocarcinoma (AD) using an array containing 2621 BAC or PAC clones spanning the genome at an average interval of 1 Mb. Array CGH identified the commonest aberrations consisting of DNA gains within 1p, 1q, 5p, 5q, 7p, 7q, 8q, 11q, 12p, 13q, 16p, 17q, 20q, and losses with 6q, 9p, 10q and 18q. High-level copy gains involved mainly 7p21-p15 and 20q13.3. Dual color fluorescence in situ hybridization (FISH) was performed on a selective locus for validation of array CGH results. Genomic aberrations were compared with different clinicopathological features and a trend of higher number of aberrations in tumors with aggressive phenotypes and current tobacco exposure was identified. According to array CGH data, 23 candidate genes were selected for quantitative PCR (qPCR) analysis. The concordance observed between the genomic and expression changes in most of the genes suggested that they could be candidate cancer-related genes that contributed to the development of lung AD.
基因组异常是癌症的标志,可能包含对癌症发生和发展至关重要的潜在候选基因。我们使用一个包含2621个BAC或PAC克隆的芯片,以平均1 Mb的间隔覆盖整个基因组,对36例原发性肺腺癌(AD)进行了芯片比较基因组杂交(array CGH)。Array CGH确定了最常见的畸变,包括1p、1q、5p、5q、7p、7q、8q、11q、12p、13q、16p、17q、20q区域的DNA增益,以及6q、9p、10q和18q区域的缺失。高水平的拷贝数增加主要涉及7p21-p15和20q13.3。对一个选择性位点进行双色荧光原位杂交(FISH)以验证array CGH结果。将基因组畸变与不同的临床病理特征进行比较,发现具有侵袭性表型和当前吸烟暴露的肿瘤中畸变数量较多的趋势。根据array CGH数据,选择了23个候选基因进行定量PCR(qPCR)分析。在大多数基因中观察到的基因组和表达变化之间的一致性表明,它们可能是导致肺腺癌发生的候选癌症相关基因。