1. ¹Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
2. ²Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3. ³Department of Biostatistical Sciences, Dana Farber Cancer Institute, Boston, MA, USA
4. ⁴Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
5. ⁵Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
6. ⁶Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA
7. ⁷Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA
8. ⁸Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: M Meyerson, Department of Medical Oncology, Dana Farber Cancer Institute, Mayer 446, 44 Binney St., Boston, MA 02115, USA. E-mail: matthew_meyerson@dfci.harvard.edu

Received 4 September 2003; Revised 29 October 2003; Accepted 30 October 2003.

Abstract

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to single-nucleotide polymorphism (SNP) arrays is an efficient method to detect genome-wide cancer LOH. Here, we survey LOH patterns in a panel of 33 human lung cancer cell lines using SNP array hybridization containing 1500 SNPs. We compared the LOH patterns generated by SNP array hybridization to those previously obtained by 399 microsatellite markers and find a high degree of concordance between the two methods. A novel informatics platform, dChipSNP, was used to perform hierarchical tumor clustering based on genome-wide LOH patterns. We demonstrate that this method can separate non-small-cell and small-cell lung cancer samples based on their shared LOH. Furthermore, we analysed seven human lung cancer cell lines using a novel 10 000 SNP array and demonstrate that this is an efficient and reliable method of high-density allelotyping. Using this array, we identified small regions of LOH that were not detected by lower density SNP arrays or by standard microsatellite marker panels.