OCGR array: an oral cancer genomic regional array for comparative genomic hybridization analysis

OCGR array: an oral cancer genomic regional array for comparative genomic hybridization analysis
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DOI:
10.1016/j.oraloncology.2003.10.006
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发表时间:
2004-05-01
期刊:
影响因子:
4.8
通讯作者:
Lam, WL
Lam, WL
中科院分区:
医学2区
文献类型:
--
作者:
Garnis, C;Campbell, J;Lam, WL

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遗传学改变已被认为是口腔鳞状细胞癌(OSCC)发生过程中的重要事件,并已被用作进展风险的预测因子。在这项研究中,我们设计了一种口腔癌特异性的人类细菌。人工染色体(BAC)阵列,称为口腔癌基因组区域阵列(OCGR),用于检测和精细定位OSCC中的拷贝数变化。这个阵列包含了总共约45 Mbp的9个与口腔癌进展有关的染色体区域。我们证明了在9个区域的每个区域的14个显微解剖的临床标本中检测到拷贝数改变。这包括拷贝数的增加和减少。虽然第一代阵列选择的区域数量很少,但我们观察到多个节段性变化。在某些情况下,我们观察到7p11和11q13分别含有EGFR和细胞周期蛋白D1的单个BAC克隆改变,这突出了对高分辨率检测技术的需求。阵列比较基因组杂交(CGH)通过将片段拷贝数改变的检测提高到单个BAC克隆分辨率,补充了检测OSCC遗传改变的传统方法(如微卫星和CGH分析)。这项工作是首次尝试构建口腔癌特异性CGH阵列。(C)2003爱思唯尔有限公司。保留所有权利。
Genetic alterations have been recognized as important events in the carcinogenesis of oral squamous cell carcinoma (OSCC) and have been used as predictors of progression risk. In this study, we have designed an oral cancer-specific human bacterial. artificial chromosome (BAC) array, called the oral cancer genomic regional array (OCGR), to detect and fine map copy number alterations in OSCC. This array contains a total of similar to45 Mbp coverage of nine chromosomal regions reported to be involved in the progression of oral cancer. We demonstrate the detection of copy number alterations in 14 microdissected clinical specimens in each of the nine regions. These include both copy number increases and decreases. Although the number of regions selected for this first generation array is small, we observed multiple segmental changes. In some cases, we observed single BAC clone alterations at 7p11 and 11q13 which contain EGFR and cyclin D1 respectively highlighting the need for high resolution detection techniques. Array comparative genomic hybridization (CGH) complements traditional methods for detecting genetic alterations in OSCC (such as microsatellite and CGH analysis) by improving the detection of segmental copy number alterations to single BAC clone resolution. This work represents the first attempt at the construction of an oral cancer-specific CGH array. (C) 2003 Elsevier Ltd. All rights reserved.