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The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice
Kenneth L Abbott1, Erik T Nyre1, Juan Abrahante1
1Department of Obstetrics, Gynecology & Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract:
Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database (CCGD, http://ccgd-starrlab.oit.umn.edu/). The CCGD is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites (CISs) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using KEGG pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The CCGD is a novel resource available to scientists interested in the identification of genetic drivers of cancer.
Insights
Identifying cancer driver genes is key for new therapies. We created the Candidate Cancer Gene Database (CCGD) to consolidate transposon mutagenesis findings, aiding cancer gene discovery.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Identifying cancer driver genes is crucial for developing targeted cancer therapies.
- Distinguishing driver mutations from passenger mutations in the human tumor genome is challenging.
- Transposon mutagenesis screens in mice have identified numerous candidate cancer driver genes, but this data is fragmented.
Purpose of the Study:
- To develop a centralized, curated database of candidate cancer driver genes identified through transposon mutagenesis.
- To improve accessibility and facilitate meta-analyses of genetic screening data for cancer research.
- To demonstrate the relevance of the curated data to human cancer pathways.
Main Methods:
- Manually curated a database of candidate driver genes and transposon common insertion sites (CISs) from published screens.
- Unified genomic locations across different mouse genome builds.
- Performed gene set enrichment analysis using KEGG pathways and hierarchical clustering.
Main Results:
- The Candidate Cancer Gene Database (CCGD) provides a unified resource of candidate cancer driver genes and CIS locations.
- Human cancer pathways were found to be significantly enriched within the CCGD.
- Hierarchical clustering revealed distinct pathways enriched in blood cancers versus solid cancers.
Conclusions:
- The CCGD is a valuable, novel resource for researchers investigating cancer genetic drivers.
- Consolidating fragmented data enhances the utility of transposon mutagenesis screens for cancer therapeutics.
- The database facilitates the identification of potential therapeutic targets by linking mouse genetic screens to human cancer pathways.
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