Multiple microalterations detected at high frequency in oral cancer
Multiple microalterations detected at high frequency in oral cancer
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DOI：
10.1158/0008-5472.can-05-1513
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发表时间：
2005-09-01
期刊：
影响因子：
11.2
通讯作者：
Lam, WL
中科院分区：
文献类型：
--
作者：
Baldwin, C;Garnis, C;Lam, WL
阵列比较基因组杂交（阵列CGH）在平铺路径分辨率的发展，使检测基因大小的片段DNA拷贝数的增益和损失。在此，我们首次将全基因组平铺路径阵列CGH应用于口腔鳞状细胞癌（OSCC）的档案临床标本中进行详细分析。我们以前所未有的细节描述了20个OSCCs的基因组以及匹配正常DNA的选择。对他们的全基因组谱的检查使他们能够确定从整个手臂、片段到基因大小变化的变化范围。平铺路径分辨率能够在每个肿瘤中检测到比以前报道的更多的改变，其中许多包括在20个OSCCs中发现的频繁事件的狭窄改变。我们报告了几种新的频繁亚兆基改变的存在，例如在45%的病例中检测到含有三重功能域（TRIO）的5p15.2的0.58 Mb增益。我们还报道了两个基因簇的首次共扩增，通过精细定位11q22.2-22.3高水平扩增的精确碱基对边界，其中包含基质金属蛋白酶和杆状病毒UP重复包含蛋白2 （BIRC）基因簇。这些结果表明，与基因组间隔标记阵列相比，检测灵敏度和分辨率有了很大的提高，并且在癌症基因发现中，平纹分辨率阵列CGH用于检测亚兆碱基和单拷贝的增益和损失。
The development of array comparative genomic hybridization (array CGH) at tiling-path resolution has enabled the detection of gene-sized segmental DNA copy number gains and losses. Here, we present the first application of whole genome tiling-path array CGH to archival clinical specimens for the detailed analysis of oral squamous cell carcinomas (OSCC). We describe the genomes of 20 OSCCs as well as a selection of matched normal DNA in unprecedented detail. Examination of their whole genome profiles enabled the identification of alterations ranging in size from whole-arm, segmental, to gene size alterations. Tiling-path resolution enabled the detection of many more alterations within each tumor than previously reported, many of which include narrow alterations found to be frequent events among the 20 OSCCs. We report the presence of several novel frequent submegabase alterations, such as the 0.58 Mb gain at 5p15.2 containing triple functional domain (TRIO), detected in 45% of cases. We also report the first coamplification of two gene clusters, by fine-mapping the precise base pair boundaries of the high-level amplification at 11q22.2-22.3 containing both matrix metalloproteinase and baculoviral UP repeat-containing protein 2 (BIRC) gene clusters. These results show the large improvement in detection sensitivity and resolution compared with genome interval marker arrays and the utility of tiling resolution array CGH for the detection of both submegabase and single copy gains and losses in cancer gene discovery.