title: Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation.
abstract: We have developed a methodology we call ROMA (representational oligonucleotide microarray analysis), for the detection of the genomic aberrations in cancer and normal humans. By arraying oligonucleotide probes designed from the human genome sequence, and hybridizing with "representations" from cancer and normal cells, we detect regions of the genome with altered "copy number." We achieve an average resolution of 30 kb throughout the genome, and resolutions as high as a probe every 15 kb are practical. We illustrate the characteristics of probes on the array and accuracy of measurements obtained using ROMA. Using this methodology, we identify variation between cancer and normal genomes, as well as between normal human genomes. In cancer genomes, we readily detect amplifications and large and small homozygous and hemizygous deletions. Between normal human genomes, we frequently detect large (100 kb to 1 Mb) deletions or duplications. Many of these changes encompass known genes. ROMA will assist in the discovery of genes and markers important in cancer, and the discovery of loci that may be important in inherited predispositions to disease.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. lucito@cshl.org
authors.forename: Robert
authors.initials: R
authors.lastname: Lucito
authors.forename: John
authors.initials: J
authors.lastname: Healy
authors.forename: Joan
authors.initials: J
authors.lastname: Alexander
authors.forename: Andrew
authors.initials: A
authors.lastname: Reiner
authors.forename: Diane
authors.initials: D
authors.lastname: Esposito
authors.forename: Maoyen
authors.initials: M
authors.lastname: Chi
authors.forename: Linda
authors.initials: L
authors.lastname: Rodgers
authors.forename: Amy
authors.initials: A
authors.lastname: Brady
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
authors.forename: Jennifer
authors.initials: J
authors.lastname: Troge
authors.forename: Joseph A
authors.initials: JA
authors.lastname: West
authors.forename: Seth
authors.initials: S
authors.lastname: Rostan
authors.forename: Ken C Q
authors.initials: KC
authors.lastname: Nguyen
authors.forename: Scott
authors.initials: S
authors.lastname: Powers
authors.forename: Kenneth Q
authors.initials: KQ
authors.lastname: Ye
authors.forename: Adam
authors.initials: A
authors.lastname: Olshen
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
mesh_terms: D000782:Aneuploidy; D001482:Base Composition / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004171:Diploidy; D005260:Female; D018628:Gene Dosage; D052138:Genes, Neoplasm / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D015345:Oligonucleotide Probes / Q000737:chemistry / Q000235:genetics; D012107:Research Design
chemical_list: D015345:Oligonucleotide Probes