RTCGD: retroviral tagged cancer gene database

Abstract

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.

Figure 1

A typical CIS List from RTCGD. Each row represents a CIS. For each CIS the retroviral integration site name (RIS name), candidate gene (by official mouse symbol), gene product description, Mouse Genome Database ID (MGI), mouse chromosomal location and number of independent retroviral integrations at the CIS with a link to the corresponding Clone List are given.

Figure 2

A typical Clone List from RTCGD. Clone names are linked to the corresponding Clone Data, which include the flanking mouse sequence and tumor data. Also included are tumor type, CIS name (RIS name), location of the integration site with respect to the candidate gene(s), distance from the candidate gene and orientation relative to the candidate gene. Genomic position data (ucsc) are linked to the UCSC mouse genome viewer with RTCGD custom annotation tracks.

Figure 3

Screenshot of the UCSC Mouse Genome Browser Version mm3 (http://genome.ucsc.edu) with RTCGD custom annotation tracks. Viral integration sites from nine groups using various different mouse tumor models are labeled by different colors and users can visually check the candidate genes for each CIS.