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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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Y. Nannya, M. Sanada, K. Nakazaki, N. Hosoya, L. Wang, A. Hangaishi, M. Kurokawa, S. Chiba, D. K. Bailey, G. C. Kennedy, et al.
A Robust Algorithm for Copy Number Detection Using High-Density Oligonucleotide Single Nucleotide Polymorphism Genotyping Arrays
Cancer Res., July 15, 2005; 65(14): 6071 - 6079.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
X. Zhao, B. A. Weir, T. LaFramboise, M. Lin, R. Beroukhim, L. Garraway, J. Beheshti, J. C. Lee, K. Naoki, W. G. Richards, et al.
Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis
Cancer Res., July 1, 2005; 65(13): 5561 - 5570.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. Hu, C. Wang, Y. Hu, H. H. Yang, C. Giffen, Z.-Z. Tang, X.-Y. Han, A. M. Goldstein, M. R. Emmert-Buck, K. H. Buetow, et al.
Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array
Cancer Res., April 1, 2005; 65(7): 2542 - 2546.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. Raghavan, D. M. Lillington, S. Skoulakis, S. Debernardi, T. Chaplin, N. J. Foot, T. A. Lister, and B. D. Young
Genome-Wide Single Nucleotide Polymorphism Analysis Reveals Frequent Partial Uniparental Disomy Due to Somatic Recombination in Acute Myeloid Leukemias
Cancer Res., January 15, 2005; 65(2): 375 - 378.
[Abstract] [Full Text] [PDF]

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 Cold Spring Harb Symp Quant BiolHome page
L.A. GARRAWAY, B.A. WEIR, X. ZHAO, H. WIDLUND, R. BEROUKHIM, A. BERGER, D. RIMM, M.A. RUBIN, D.E. FISHER, M.L. MEYERSON, et al.
"Lineage Addiction" in Human Cancer: Lessons from Integrated Genomics
Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 25 - 34.
[Abstract] [PDF]

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 Eukaryot CellHome page
A. Forche, G. May, and P. T. Magee
Demonstration of Loss of Heterozygosity by Single-Nucleotide Polymorphism Microarray Analysis and Alterations in Strain Morphology in Candida albicans Strains during Infection
Eukaryot. Cell, January 1, 2005; 4(1): 156 - 165.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. T. Barrett, A. Scheffer, A. Ben-Dor, N. Sampas, D. Lipson, R. Kincaid, P. Tsang, B. Curry, K. Baird, P. S. Meltzer, et al.
Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA
PNAS, December 21, 2004; 101(51): 17765 - 17770.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
J. Cardoso, L. Molenaar, R. X. de Menezes, C. Rosenberg, H. Morreau, G. Moslein, R. Fodde, and J. M. Boer
Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH
Nucleic Acids Res., October 28, 2004; 32(19): e146 - e146.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
T. Tengs, T. LaFramboise, R. B. Den, D. N. Hayes, J. Zhang, S. DebRoy, R. C. Gentleman, K. O'Neill, B. Birren, and M. Meyerson
Genomic representations using concatenates of Type IIB restriction endonuclease digestion fragments
Nucleic Acids Res., August 25, 2004; 32(15): e121 - e121.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. Brennan, Y. Zhang, C. Leo, B. Feng, C. Cauwels, A. J. Aguirre, M. Kim, A. Protopopov, and L. Chin
High-Resolution Global Profiling of Genomic Alterations with Long Oligonucleotide Microarray
Cancer Res., July 15, 2004; 64(14): 4744 - 4748.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
J. G. Paez, M. Lin, R. Beroukhim, J. C. Lee, X. Zhao, D. J. Richter, S. Gabriel, P. Herman, H. Sasaki, D. Altshuler, et al.
Genome coverage and sequence fidelity of {phi}29 polymerase-based multiple strand displacement whole genome amplification
Nucleic Acids Res., May 18, 2004; 32(9): e71 - e71.
[Abstract] [Full Text] [PDF]


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