High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines

Abstract

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to singlenucleotide 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.

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

“…In addition, relevant to the current study, SNP arrays are able to cluster lung cancer samples to different subtypes based on their shared regions of LOH [37]. Further, high-density SNP arrays can be used to infer chromosomal copy number changes (i.e.…”

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

“…Polymerase chain reaction (PCR)-based measurement of simple sequence length polymorphisms is a reliable method for detecting LOH, but is both expensive and labor intensive. Recently, global and high-resolution analyses of LOH using single-nucleotide polymorphism (SNP) arrays, which was originally designed for high-throughput SNP analysis (Wang et al, 1998;Kennedy et al, 2003), have been performed in various cancers (Lindblad-Toh et al, 2000;Mei et al, 2000;Lieberfarb et al, 2003;Janne et al, 2004). Comparing this method to PCR-based microsatellite analysis directly, Hoque et al (2003) validated the accuracy of LOH analysis using SNP arrays.…”

Expression of the FAM5C in tongue squamous cell carcinoma

“…Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of TSGs in human carcinoma. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers (1).…”

“…Several studies have successfully utilized this array for identifying consistent LOH regions in breast cancer (4)(5)(6)(7)(8), bladder cancer (9,10), prostate cancer (11,12), osteosarcoma (13), lung cancer (1,14) and oral SCC-derived cell lines (3,15). However, only a limited number of studies have utilized this assay for identifying consistent LOH regions in human oral SCCs.…”