Cowell John K, Hawthorn Lesleyann
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Curr Mol Med. 2007 Feb;7(1):103-20. doi: 10.2174/156652407779940387.
The identification of genetic events that are involved in the development of human cancer has been facilitated through the development and application of a diverse series of high resolution, high throughput microarray platforms. Essentially there are two types of array; those that carry PCR products from cloned nucleic acids (e.g. cDNA, BACs, cosmids) and those that use oligonucleotides. Each has advantages and disadvantages but it is now possible to survey genome wide DNA copy number abnormalities and expression levels to allow correlations between losses, gains and amplifications in tumor cells with genes that are over- and under-expressed in the same samples. The gene expression arrays that provide estimates of mRNA levels in tumors have given rise to exon-specific arrays that can identify both gene expression levels, alternative splicing events and mRNA processing alterations. Oligonucleotide arrays are also being used to interrogate single nucleotide polymorphisms (SNPs) throughout the genome for linkage and association studies and these have been adapted to quantify copy number abnormalities and loss of heterozygosity events. To identify as yet unknown transcripts tiling arrays across the genome have been developed which can also identify DNA methylation changes and be used to identify DNA-protein interactions using ChIP on Chip protocols. Ultimately DNA sequencing arrays will allow resequencing of chromosome regions and whole genomes. With all of these capabilities becoming routine in genomics laboratories, the idea of a systematic characterization of the sum genetic events that give rise to a cancer cell is rapidly becoming a reality.
通过开发和应用一系列多样的高分辨率、高通量微阵列平台，人们对参与人类癌症发生发展的遗传事件的识别得到了促进。基本上有两种类型的阵列：一种携带来自克隆核酸（如cDNA、BAC、黏粒）的PCR产物，另一种使用寡核苷酸。每种都有优缺点，但现在有可能在全基因组范围内检测DNA拷贝数异常和表达水平，以便将肿瘤细胞中的缺失、增加和扩增与同一样本中过表达和低表达的基因进行关联。提供肿瘤中mRNA水平估计值的基因表达阵列已衍生出可识别基因表达水平、可变剪接事件和mRNA加工改变的外显子特异性阵列。寡核苷酸阵列也正被用于在全基因组范围内检测单核苷酸多态性（SNP）以进行连锁和关联研究，并且这些阵列已被改编用于量化拷贝数异常和杂合性缺失事件。为了识别尚未知晓的转录本，已经开发出覆盖全基因组的平铺阵列，其也可以识别DNA甲基化变化，并用于通过芯片上的染色质免疫沉淀（ChIP）协议识别DNA - 蛋白质相互作用。最终，DNA测序阵列将允许对染色体区域和全基因组进行重测序。随着所有这些能力在基因组学实验室中变得常规化，对导致癌细胞产生的所有遗传事件进行系统表征的想法正迅速成为现实。
