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The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice

机译:候选癌症基因数据库:来自小鼠正向遗传筛选的癌症驱动基因数据库

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摘要

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, ). 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.
机译:癌症驱动基因突变的鉴定对于推进癌症治疗至关重要。由于人类肿瘤基因组中大量的客体突变,很难确定致病性驱动基因。利用小鼠中的转座子诱变,许多实验室已经进行了正向遗传筛选,并鉴定了数千种与人类癌症高度相关的候选驱动基因。不幸的是,该信息难以访问和利用,因为它散布在使用不同小鼠基因组构建和强度指标的多个出版物中。为了改善对这些发现的访问并促进荟萃分析,我们开发了候选癌症基因数据库(CCGD,)。 CCGD是一个手动管理的数据库,其中包含所有已发布的基于转座子的筛选中所有已鉴定的候选驱动基因和转座子共同插入位点(CIS)的基因组位置的统一描述。为了证明与人类癌症的相关性,我们使用KEGG途径进行了改良的基因集富集分析,并显示了人类癌症途径在数据库中高度富集。我们还使用层次聚类来确定与实体癌相比富含血液癌的途径。 CCGD是一种新颖的资源,可供对识别癌症的遗传驱动因素感兴趣的科学家使用。

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