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

2004; American Association for Cancer Research; Volume: 64; Issue: 9 Linguagem: Inglês

10.1158/0008-5472.can-03-3308

1538-7445

Xiaojun Zhao, Cheng Li, J. Guillermo Paez, Koei Chin, Pasi A. Jänne, Tzu-Hsiu Chen, Luc Girard, John D. Minna, David C. Christiani, Chris Leo, Joe W. Gray, William R. Sellers, Matthew Meyerson,

Chromosomal and Genetic Variations

Abstract 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.