Akagi Keiko, Suzuki Takeshi, Stephens Robert M, Jenkins Nancy A, Copeland Neal G
Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21701, USA.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D523-7. doi: 10.1093/nar/gkh013.
Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a potent cancer gene discovery tool in the post-genome-sequence era. To manage multiple high-throughput insertional mutagenesis screening projects, we developed the Retroviral Tagged Cancer Gene Database (RTCGD; http://RTCGD.ncifcrf.gov). A sequence analysis pipeline determines the genomic position of each retroviral integration site cloned from a mouse tumor, the distance between it and the nearest candidate disease gene(s) and its orientation with respect to the candidate gene(s). The pipeline also identifies genomic regions that are targets of retroviral integration in more than one tumor (common integration sites, CISs) and are thus likely to encode a disease gene. Users can search the database using a specified gene symbol, chromosome number or tumor model to identify both CIS genes and unique viral integration sites or compare the integration sites cloned by different laboratories using different models. As a default setting, users first review the CIS Lists and then Clone Lists. CIS Lists describe CISs and their candidate disease genes along with links to other public databases and clone lists. Clone Lists describe the viral integration site clones along with the tumor model and tumor type from which they were cloned, candidate disease gene(s), genomic position and orientation of the integrated provirus with respect to the candidate gene(s). It also provides a pictorial view of the genomic location of each integration site relative to neighboring genes and markers. Researchers can identify integrations of interest and compare their results with those for multiple tumor models and tumor types using RTCGD.
逆转录病毒插入诱变在小鼠造血肿瘤中为后基因组序列时代提供了一种强大的癌症基因发现工具。为管理多个高通量插入诱变筛选项目,我们开发了逆转录病毒标记癌症基因数据库(RTCGD;http://RTCGD.ncifcrf.gov)。一个序列分析流程可确定从小鼠肿瘤中克隆的每个逆转录病毒整合位点的基因组位置、它与最近候选疾病基因之间的距离以及其相对于候选基因的方向。该流程还能识别在不止一个肿瘤中作为逆转录病毒整合靶点的基因组区域(共同整合位点,CISs),因此这些区域可能编码一个疾病基因。用户可以使用指定的基因符号、染色体编号或肿瘤模型搜索数据库,以识别CIS基因和独特的病毒整合位点,或者比较不同实验室使用不同模型克隆的整合位点。作为默认设置,用户首先查看CIS列表,然后查看克隆列表。CIS列表描述了CIS及其候选疾病基因,以及指向其他公共数据库和克隆列表的链接。克隆列表描述了病毒整合位点克隆,以及它们所克隆自的肿瘤模型和肿瘤类型、候选疾病基因、整合前病毒相对于候选基因的基因组位置和方向。它还提供了每个整合位点相对于相邻基因和标记的基因组位置的图示。研究人员可以使用RTCGD识别感兴趣的整合,并将他们的结果与多个肿瘤模型和肿瘤类型的结果进行比较。