Novel Candidate Cancer Genes Identified by a Large-Scale Cross-Species Comparative Oncogenomics Approach
Novel Candidate Cancer Genes Identified by a Large-Scale Cross-Species Comparative Oncogenomics Approach
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DOI：
10.1158/0008-5472.can-09-1737
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发表时间：
2010-02-01
期刊：
影响因子：
11.2
通讯作者：
Adams, David J.
中科院分区：
文献类型：
--
作者：
Mattison, Jenny;Kool, Jaap;Adams, David J.
比较基因组杂交（CGH）可以揭示重要的疾病基因，但确定的大区域有时可能包含数百个基因。在这里，我们结合联合收割机高分辨率CGH分析598人类癌细胞系与插入位点分离自1,005小鼠肿瘤诱导的小鼠白血病病毒（MuLV）。这种跨物种的癌基因组分析揭示了候选肿瘤抑制基因和癌基因在人类和小鼠肿瘤中的突变，使它们成为新癌症基因的强有力候选者。这些基因中有相当数量含有干细胞转录因子Oct 4和Nanog的结合位点。值得注意的是，携带在干细胞模块基因中或附近插入的肿瘤的小鼠，被认为参与细胞自我更新，比没有这些插入的小鼠死得更快。我们确定的配置文件的比较，诱导与睡美人（SB）转座子系统揭示了显着的差异，反复突变的基因的配置文件。总的来说，这项工作为功能分析提供了丰富的新候选癌症基因目录。Cancer Res; 70（3）; 883-95.（C）2010年AACR。
Comparative genomic hybridization (CGH) can reveal important disease genes but the large regions identified could sometimes contain hundreds of genes. Here we combine high-resolution CGH analysis of 598 human cancer cell lines with insertion sites isolated from 1,005 mouse tumors induced with the murine leukemia virus (MuLV). This cross-species oncogenomic analysis revealed candidate tumor suppressor genes and oncogenes mutated in both human and mouse tumors, making them strong candidates for novel cancer genes. A significant number of these genes contained binding sites for the stem cell transcription factors Oct4 and Nanog. Notably, mice carrying tumors with insertions in or near stem cell module genes, which are thought to participate in cell self-renewal, died significantly faster than mice without these insertions. A comparison of the profile we identified to that induced with the Sleeping Beauty (SB) transposon system revealed significant differences in the profile of recurrently mutated genes. Collectively, this work provides a rich catalogue of new candidate cancer genes for functional analysis. Cancer Res; 70(3); 883-95. (C)2010 AACR.