title: Genome-wide detection of allelic imbalance using human SNPs and high-density DNA arrays.
abstract: Most human cancers are characterized by genomic instability, the accumulation of multiple genetic alterations and allelic imbalance throughout the genome. 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. Here we describe the use of high-density oligonucleotide arrays for genome-wide scans for LOH and allelic imbalance in human tumors. The arrays contain redundant sets of probes for 600 genetic loci that are distributed across all 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 heterogeneous 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 allelic imbalance with potential prognostic and diagnostic utility.
authors.affiliation: Affymetrix, Inc., Santa Clara, California 95051, USA. rui_mei@affymetrix.com
authors.forename: R
authors.initials: R
authors.lastname: Mei
authors.forename: P C
authors.initials: PC
authors.lastname: Galipeau
authors.forename: C
authors.initials: C
authors.lastname: Prass
authors.forename: A
authors.initials: A
authors.lastname: Berno
authors.forename: G
authors.initials: G
authors.lastname: Ghandour
authors.forename: N
authors.initials: N
authors.lastname: Patil
authors.forename: R K
authors.initials: RK
authors.lastname: Wolff
authors.forename: M S
authors.initials: MS
authors.lastname: Chee
authors.forename: B J
authors.initials: BJ
authors.lastname: Reid
authors.forename: D J
authors.initials: DJ
authors.lastname: Lockhart
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods* / Q000706:statistics & numerical data; D004938:Esophageal Neoplasms / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results