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Analysis of copy number abnormality (CNA) and loss of heterozygosity (LOH) in the whole genome using single nucleotide polymorphism (SNP) genotyping arrays in tongue squamous cell carcinoma

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Tsukasa Kuroiwa, Nobuharu Yamamoto, Takeshi Onda, Hiroki Bessyo, Takashi Yakushiji, Akira Katakura, Nobuo Takano, Takahiko Shibahara,
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 ( Tsukasa Kuroiwa ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Nobuharu Yamamoto ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Takeshi Onda ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Hiroki Bessyo ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Takashi Yakushiji ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Akira Katakura ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Nobuo Takano ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery
 ( Takahiko Shibahara ) - Tokyo Dental College Department of Oral and Maxillofacial Surgery

Abstract


Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers; however, owing to the limited number of available microsatellite markers and the requirement for large amounts of DNA, only a modest number of microsatellite markers can be screened. Hybridization to single nucleotide polymorphism (SNP) arrays using Affymetarix GeneChip Mapping 10 K 2.0 Array is an efficient method to detect genome-wide cancer LOH. We determined the presence of LOH in oral SCCs using these arrays. DNA was extracted from tissue samples obtained from 10 patients with tongue SCCs who presented at the Hospital of Tokyo Dental College. We examined the presence of LOH in 3 of the 10 patients using these arrays. At the locus that had LOH, we examined the presence of LOH using microsatellite markers. LOH analysis using Affymetarix GeneChip Mapping 10K Array showed LOH in all patients at the 1q31.1. The LOH regions were detected and demarcated by the copy number 1 with the series of three SNP probes. LOH analysis of 1q31.1 using microsatellite markers (D1S1189, D1S2151, D1S2595) showed LOH in all 10 patients (100). Our data may suggest that a putative tumor suppressor gene is located at the 1q31.1 region. Inactivation of such a gene may play a role in tongue tumorigenesis.

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Tongue squamous cell carcinoma; Loss of heterozygosity; Copy number abnormality; Single nucleotide polymorphism; tumor suppressor gene

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