Whole genome loss of heterozygosity profiling on oral squamous cell carcinoma by high-density single nucleotide polymorphic allele (SNP) array

Abstract

Most human cancers are characterized by genetic instabilities [ [1] Lengauer C Kinzler K.W Vogelstein B Genetic instabilities in human cancers. Nature. 1998; 396: 643-649 Crossref PubMed Scopus (3367) Google Scholar ]. Chromosomal aberrations include segments of allelic imbalance identifiable by loss of heterozygosity (LOH) at polymorphic loci, which may be used to implicate regions harboring tumor suppressor genes [ 2 Pekarsky Y Palamarchuk A Huebner K Croce C.M FHIT as tumor suppressor: mechanisms and therapeutic opportunities. Cancer Biol Ther. 2002; 1: 232-236 PubMed Google Scholar , 3 Zabarovsky E.R Lerman M.I Minna J.D Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene. 2002; 21: 6915-6935 Crossref PubMed Scopus (324) Google Scholar , 4 Dong J.T Chromosomal deletions and tumor suppressor genes in prostate cancer. Cancer Metastasis Rev. 2001; 20: 173-193 Crossref PubMed Scopus (177) Google Scholar ]. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers; however, due to the limited number of available microsatellite markers, the rather tedious and labor-intensive procedure, and the requirement for large amounts of DNA, only a modest number of microsatellite makers can be screened. High-density whole genome allelotyping cannot be performed. Single nucleotide polymorphisms (SNPs) offer many advantages for genetic analysis, including their prevalence in the genome and the ease of assay. The unique advantage of SNPs for LOH analysis is that, unlike microsatellites, they are not susceptible to the repeat expansion that is so often observed in cancer [ 5 Serakinci N Pedersen B Koch J Expansion of repetitive DNA into cytogenetically visible elements. Cytogenet Cell Genet. 2001; 92: 182-185 Crossref PubMed Scopus (5) Google Scholar , 6 Panzer S Kuhl D.P Caskey C.T Unstable triplet repeat sequences: a source of cancer mutations?. Stem Cells. 1995; 13: 146-157 Crossref PubMed Scopus (24) Google Scholar , 7 Richetta A Ottini L Falchetti M Innocenzi D Bottoni U Faiola R Mariani-Costantini R Calvieri S Instability at sequence repeats in melanocytic tumours. Melanoma Res. 2001; 11: 283-289 Crossref PubMed Scopus (24) Google Scholar ] and thus provide higher-fidelity markers for tracking the fate of chromosome segments. SNP-based LOH analysis is therefore the most logical approach for genome-wide allelic imbalance profiling. Recently, several studies have successfully utilized the Affymetrix (Santa Clara, CA) HuSNP GeneChip, which contains 1494 SNPs for identifying consistent LOH regions in small cell lung, breast, bladder, and prostate cancer [ 8 Lindblad-Toh K Tanenbaum D.M Daly M.J Winchester E Lui W.O Villapakkam A Stanton S.E Larsson C Hudson T.J Johnson B.E Lander E.S Meyerson M Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays. Nat Biotechnol. 2000; 18: 1001-1005 Crossref PubMed Scopus (240) Google Scholar , 9 Schubert E.L Hsu L Cousens L.A Glogovac J Self S Reid B.J Rabinovitch P.S Porter P.L Single nucleotide polymorphism array analysis of flow-sorted epithelial cells from frozen versus fixed tissues for whole genome analysis of allelic loss in breast cancer. Am J Pathol. 2002; 160: 73-79 Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar , 10 Dumur C.I Dechsukhum C Ware J.L Cofield S.S Best A.M Wilkinson D.S Garrett C.T Ferreira-Gonzalez A Genome-wide detection of LOH in prostate cancer using human SNP microarray technology. Genomics. 2003; 81: 260-269 Crossref PubMed Scopus (81) Google Scholar , 11 Hoque M.O Lee C.C Cairns P Schoenberg M Sidransky D Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis. Cancer Res. 2003; 63: 2216-2222 PubMed Google Scholar , 12 Primdahl H Wikman F.P von der Maase H Zhou X.G Wolf H Orntoft T.F Allelic imbalances in human bladder cancer: genome-wide detection with high-density single-nucleotide polymorphism arrays. J Natl Cancer Inst. 2002; 94: 216-223 Crossref PubMed Scopus (85) Google Scholar ].