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1 Departments of Medical Oncology and 2 Biostatistical Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts; 3 Departments of Medicine and 4 Pathology, Harvard Medical School, Boston, Massachusetts; 5 Departments of Biostatistics and 6 Environmental Health, Harvard School of Public Health, Boston, Massachusetts; 7 Department of Laboratory Medicine, University of California, San Francisco, California, 8 Hamon Center for Therapeutic Oncology Research, and 9 Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas
Changes in DNA copy number contribute to cancer pathogenesis. We now show that high-density single nucleotide polymorphism (SNP) arrays can detect copy number alterations. By hybridizing genomic representations of breast and lung carcinoma cell line and lung tumor DNA to SNP arrays, and measuring locus-specific hybridization intensity, we detected both known and novel genomic amplifications and homozygous deletions in these cancer samples. Moreover, by combining genotyping with SNP quantitation, we could distinguish loss of heterozygosity events caused by hemizygous deletion from those that occur by copy-neutral events. The simultaneous measurement of DNA copy number changes and loss of heterozygosity events by SNP arrays should strengthen our ability to discover cancer-causing genes and to refine cancer diagnosis.
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