The application of microarray technology to the analysis of the cancer genome

Abstract

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.