Prognostic significance of genetic alterations detected by high‐density single nucleotide polymorphism array in gastric cancer
Prognostic significance of genetic alterations detected by high‐density single nucleotide polymorphism array in gastric cancer
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DOI：
10.1111/j.1349-7006.2010.01500.x
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发表时间：
2010-05
期刊：
影响因子：
5.7
通讯作者：
Motohisa Tada;F. Kanai;Yasuo Tanaka;M. Sanada;Y. Nannya;K. Tateishi;M. Ohta;Yoshinari Asaoka;Motoko Seto;F. Imazeki;H. Yoshida;S. Ogawa;O. Yokosuka;M. Omata
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作者：
Motohisa Tada;F. Kanai;Yasuo Tanaka;M. Sanada;Y. Nannya;K. Tateishi;M. Ohta;Yoshinari Asaoka;Motoko Seto;F. Imazeki;H. Yoshida;S. Ogawa;O. Yokosuka;M. Omata
我们试图识别可能对临床应用有用的基因组变化，重点关注染色体不稳定性并使用高密度单核苷酸多态性（SNP）阵列。我们使用 Affymetrix GeneChip Human Mapping 50 K Arrays 分析了 34 个胃癌细胞系中表现出拷贝数变化的 DNA 区域。使用基因组 PCR、定量实时 PCR 和杂合性丢失 (LOH) 分析在 42 个胃癌组织中验证了细胞系获得的结果。在胃癌细胞系中发现了 26 个局部纯合缺失区域，包括 13 个新基因座，以及 31 个重复性高级别增益区域，包括 14 个新基因座。在细胞系中检测到的高级别增益基因中，MYC、PAK1 和 ITGB4BP 在超过 40% 的胃癌组织中显示出拷贝数增益。在超过35%的胃癌组织中检测到AB051467、PTPRD、A2BP1和C20orf133的LOH。有淋巴结转移的肿瘤中 LOH 的数量明显较多。早期，少于2个基因的LOH患者的预后明显好于2个及以上基因的LOH患者。使用高密度 SNP 阵列，我们发现了一些新颖且微小的基因组改变。四个基因的LOH可用于预测早期胃癌的淋巴结转移和预后。
We sought to identify genomic changes that could be useful for clinical application, focusing on chromosomal instability and using a high‐density single nucleotide polymorphism (SNP) array. We analyzed 34 gastric cancer cell lines for areas of DNA that exhibited copy number changes using the Affymetrix GeneChip Human Mapping 50 K Arrays. The results obtained with the cell lines were verified in 42 gastric cancer tissues using genomic PCR, quantitative real‐time PCR, and loss of heterozygosity (LOH) analyses. Twenty‐six local homozygous deletion regions, including 13 novel loci, and 31 recurrent high‐grade gain regions, encompassing 14 novel loci, were found in the gastric cancer cell lines. Among the genes detected for high‐grade gain in the cell lines, MYC, PAK1, and ITGB4BP showed copy number gain in more than 40% of gastric cancer tissues. LOH of AB051467, PTPRD, A2BP1, and C20orf133 was detected in more than 35% of gastric cancer tissues. The number of LOH was significantly greater in tumors with lymph node metastasis. In the early stage, the prognosis of patients with LOH of less than two genes was significantly better than that of those with LOH of two genes or more. Using high‐density SNP arrays, we identified several novel and minute genomic alterations. LOH of four genes could be useful for prediction of lymph node metastasis and prognosis in early stage gastric cancers.