title: High-resolution analysis of DNA copy number using oligonucleotide microarrays.
abstract: Genomic copy number alterations are a feature of many human diseases including cancer. We have evaluated the effectiveness of an oligonucleotide array, originally designed to detect single-nucleotide polymorphisms, to assess DNA copy number. We first showed that fluorescent signal from the oligonucleotide array varies in proportion to both decreases and increases in copy number. Subsequently we applied the system to a series of 20 cancer cell lines. All of the putative homozygous deletions (10) and high-level amplifications (12; putative copy number >4) tested were confirmed by PCR (either qPCR or normal PCR) analysis. Low-level copy number changes for two of the lines under analysis were compared with BAC array CGH; 77% (n = 44) of the autosomal chromosomes used in the comparison showed consistent patterns of LOH (loss of heterozygosity) and low-level amplification. Of the remaining 10 comparisons that were discordant, eight were caused by low SNP densities and failed in both lines. The studies demonstrate that combining the genotype and copy number analyses gives greater insight into the underlying genetic alterations in cancer cells with identification of complex events including loss and reduplication of loci.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Bignell
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: Adam
authors.initials: A
authors.lastname: Butler
authors.forename: Sofie
authors.initials: S
authors.lastname: West
authors.forename: Mira
authors.initials: M
authors.lastname: Grigorova
authors.forename: Keith W
authors.initials: KW
authors.lastname: Jones
authors.forename: Wen
authors.initials: W
authors.lastname: Wei
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Barbara
authors.initials: B
authors.lastname: Weber
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shapero
authors.forename: Richard
authors.initials: R
authors.lastname: Wooster
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D018628:Gene Dosage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000639:trends; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D004247:DNA