Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine  AACR Conference on Molecular Diagnostics
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[Cancer Research 64, 3060-3071, May 1, 2004]
© 2004 American Association for Cancer Research


Regular Articles

An Integrated View of Copy Number and Allelic Alterations in the Cancer Genome Using Single Nucleotide Polymorphism Arrays

Xiaojun Zhao1,4, Cheng Li2,5, J. Guillermo Paez1,3, Koei Chin7, Pasi A. Jänne1,3, Tzu-Hsiu Chen1, Luc Girard8,9, John Minna8,9, David Christiani6, Chris Leo1, Joe W. Gray7, William R. Sellers1,3 and Matthew Meyerson1,4

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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Copyright © 2004 by the American Association for Cancer Research.