Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation.
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.
Lucito
Robert
R
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. lucito@cshl.org
Healy
John
J
Alexander
Joan
J
Reiner
Andrew
A
Esposito
Diane
D
Chi
Maoyen
M
Rodgers
Linda
L
Brady
Amy
A
Sebat
Jonathan
J
Troge
Jennifer
J
West
Joseph A
JA
Rostan
Seth
S
Nguyen
Ken C Q
KC
Powers
Scott
S
Ye
Kenneth Q
KQ
Olshen
Adam
A
Venkatraman
Ennapadam
E
Norton
Larry
L
Wigler
Michael
M
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
D015345:Oligonucleotide Probes