Nature Biotechnology
18, 1001 - 1005 (2000)
doi:10.1038/79269
Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arraysKerstin Lindblad-Toh1, 8, David M. Tanenbaum2, 3, 4, 8, Mark J. Daly1, Ellen Winchester1, Weng-Onn Lui5, Anuradha Villapakkam1, Sasha E. Stanton2, Catharina Larsson5, Thomas J. Hudson1, 6, Bruce E. Johnson2, 3, Eric S. Lander1, 7
& Matthew Meyerson2, 41
Whitehead Institute/MIT Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02139. 2
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA. 3
Department of Medicine, Harvard Medical School, Boston, MA. 4
Department of Pathology, Harvard Medical School, Boston, MA. 5
Department of Molecular Medicine, CMM, Karolinska Hospital, Stockholm, S-171 76 Sweden. 6
Montreal Genome Centre, McGill University Health Centre, Montréal, Québec. 7
Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02142. 8
These two authors contributed equally to this work.
Correspondence should be addressed to Eric S. Lander lander@genome.wi.mit.edu or Matthew Meyerson matthew_meyerson@dfci.harvard.eduHuman cancers arise by a combination of discrete mutations and chromosomal alterations. Loss of heterozygosity (LOH) of chromosomal regions bearing mutated tumor suppressor genes is a key event in the evolution of epithelial and mesenchymal tumors1. Global patterns of LOH can be understood through allelotyping of tumors with polymorphic genetic markers2. Simple sequence length polymorphisms (SSLPs, or microsatellites) are reliable genetic markers for studying LOH3, but only a modest number of SSLPs are used in LOH studies because the genotyping procedure is rather tedious. Here, we report the use of a highly parallel approach to genotype large numbers of single-nucleotide polymorphisms (SNPs) for LOH, in which samples are genotyped for nearly 1,500 loci by performing 24 polymerase chain reactions (PCR), pooling the resulting amplification products and hybridizing the mixture to a high-density oligonucleotide array4. We characterize the results of LOH analyses on human small-cell lung cancer (SCLC) and control DNA samples by hybridization. We show that the patterns of LOH are consistent with those obtained by analysis with both SSLPs5 and comparative genomic hybridization (CGH), whereas amplifications rarely are detected by the SNP array. The results validate the use of SNP array hybridization for tumor studies.
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