High-resolution global profiling of genomic alterations with long oligonucleotide microarray
High-resolution global profiling of genomic alterations with long oligonucleotide microarray
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DOI：
10.1158/0008-5472.can-04-1241
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发表时间：
2004-07-15
期刊：
影响因子：
11.2
通讯作者：
Chin, L
中科院分区：
文献类型：
--
作者：
Brennan, C;Zhang, YY;Chin, L
癌症代表了多种遗传损伤的表型终点，这些损伤赋予细胞肿瘤发生所需的全面生物学特性。癌症基因组的标志性特征之一是反复出现的区域性得失，经过详细的表征，这些得失为新的癌基因和肿瘤抑制基因提供了高效的发现途径。在这项研究中，我们描述了基于寡核苷酸的微阵列平台的使用，以及必要的分析条件和生物信息挖掘工具的开发，从而实现了对人类和小鼠肿瘤的高分辨率全基因组阵列-比较基因组杂交图谱。使用商业上可用的60聚体寡核苷酸微阵列，我们证明了该平台在提供高分辨率的同时，提供了足够的灵敏度来检测全复杂性基因组DNA的单拷贝差异。微阵列和相关试剂的商业可获得性，以及本报告所述的技术方案和分析工具，应使研究人员能够立即以全球和详细的方式对正常和疾病基因组进行DNA分析。
Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a full range of biological properties required for tumorigenesis. Among the hallmark features of the cancer genome are recurrent regional gains and losses that, upon detailed characterization, have provided highly productive discovery paths for new oncogenes and tumor suppressor genes. In this study, we describe the use of an oligonucleotide-based microarray platform and development of requisite assay conditions and bioinformatic mining tools that permits high-resolution genome-wide array-comparative genome hybridization profiling of human and mouse tumors. Using a commercially available 60-mer oligonucleotide microarray, we demonstrate that this platform provides sufficient sensitivity to detect single-copy difference in gene dosage of full complexity genomic DNA while offering high resolution. The commercial availability of the microarrays and associated reagents, along with the technical protocols and analytical tools described in this report, should provide investigators with the immediate capacity to perform DNA analysis of normal and diseased genomes in a global and detailed manner.