Genome-wide detection of allelic imbalance using human SNPs and high-density DNA arrays

Most human cancers are characterized by genomic instability, the accumulati on of multiple genetic alterations and allelic imbalance throughout the gen ome. Loss of heterozygosity (LOH) is a common form of allelic imbalance and the detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize tumor stages and progression. H ere we describe the use of high-density oligonucleotide arrays for genome-w ide scans for LOH and allelic imbalance in human tumors. The arrays contain redundant sets of probes for 600 genetic loci that are distributed across ail human chromosomes. The arrays were used to detect allelic imbalance in two types of human tumors, and a subset of the results was confirmed using conventional gel-based methods. We also tested the ability to study heterog eneous cell populations and found that allelic imbalance can be detected in the presence of a substantial background of normal cells. The detection of LOH and other chromosomal changes using large numbers of single nucleotide polymorphism (SNP) markers should enable identification of patterns of all elic imbalance with potential prognostic and diagnostic utility.