Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array

Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array
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DOI:
10.1159/000155813
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发表时间:
2008-01-01
期刊:
影响因子:
3.5
通讯作者:
Omata, Masao
Omata, Masao
中科院分区:
医学3区
文献类型:
--
作者:
Lin, Lian-Jie;Asaoka, Yoshinari;Omata, Masao

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目的:探讨胰腺癌的分子遗传事件。方法:我们使用高密度单核苷酸多态性(SNP)阵列分析了25个已建立的胰腺癌细胞系的全基因组拷贝数改变和杂合性缺失(LOH)。我们使用基因组PCR验证了这些数据,并将其应用于临床样本。结果:在至少1株细胞系中检测到26个纯合缺失区,在9p、18q、17p、8p、13q、6q、3p、6p、22q、9q、12q处发现LOH,且频率高(约50%),与前人研究一致。此外,我们在至少2个细胞系中发现了23个扩增区域,其中包括8个未报道的位点。然后,我们在匹配的胰腺癌和正常组织中检测了8个扩增位点的代表性基因。14例显微解剖组织标本中有1例(7.1%)~ 5例(35.7%)存在扩增。结论:利用高分辨率SNP阵列,我们同时研究了全基因组拷贝数改变和LOH。我们确定了几个新的和微小的基因组扩增,其中包含人类胰腺癌的候选癌基因。版权所有2008 S. Karger AG,巴塞尔
Objective: To chart molecular genetic events in pancreatic cancer. Methods: We analyzed genome-wide copy number alterations and loss of heterozygosity (LOH) in 25 established pancreatic cancer cell lines using a high-density single nucleotide polymorphism ( SNP) array. We verified the data using genomic PCR and applied them to clinical samples. Results: Twenty-six homozygous deletion regions were detected in at least 1 cell line and LOH was found at 9p, 18q, 17p, 8p, 13q, 6q, 3p, 6p, 22q, 9q and 12q with high frequency (> 50%), consistent with a previous study. Moreover, we found 23 amplified regions in at least 2 cell lines, including 8 unreported loci. We then examined representative genes at the 8 amplified loci in matched pairs of pancreatic cancer and normal tissues. The amplification was detected in 1 (7.1%) to 5 (35.7%) of 14 microdissected tissue specimens. Conclusion: Using high-resolution SNP arrays, we studied genome-wide copy number alterations and LOH simultaneously. We identified several novel and minute genomic amplifications, which contained candidate oncogenes in human pancreatic cancers. Copyright (C) 2008 S. Karger AG, Basel.