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Published online before print September 15, 2003, 10.1101/gr.1349003
Genome Res. 13:2291-2305, 2003
©2003 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/03 $5.00
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Letter

Representational Oligonucleotide Microarray Analysis: A High-Resolution Method to Detect Genome Copy Number Variation

Robert Lucito1,5, John Healy1, Joan Alexander1, Andrew Reiner1, Diane Esposito1, Maoyen Chi1, Linda Rodgers1, Amy Brady1, Jonathan Sebat1, Jennifer Troge1, Joseph A. West1, Seth Rostan1, Ken C.Q. Nguyen2, Scott Powers1,2, Kenneth Q. Ye3, Adam Olshen4, Ennapadam Venkatraman4, Larry Norton4 and Michael Wigler1

1 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA 2 Tularik Inc., Genomics Division, Greenlawn, New York 11740, USA 3 Department of Applied Math and Statistics, SUNY at Stony Brook, Stony Brook, New York 11794, USA 4 Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA

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.

5 Corresponding author.
E-MAIL lucito{at}cshl.org; FAX (516)367-8381.

[The photoprint arrays were a kind gift of NimbleGen Systems Inc. and were fabricated to our design.]

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1349003. Article published online before print in September 2003.


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