Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Pancreas. 2013 Aug;42(6):1016-26. doi: 10.1097/MPA.0b013e318287d043.
This study used an integrated analysis of copy number, gene expression, and RNA interference screens for identification of putative driver genes harbored in somatic copy number gains in pancreatic ductal adenocarcinoma (PDAC).
Somatic copy number gain data on 60 PDAC genomes were extracted from public data sets to identify genomic loci that are recurrently gained. Array-based data from a panel of 29 human PDAC cell lines were used to quantify associations between copy number and gene expression for the set of genes found in somatic copy number gains. The most highly correlated genes were assessed in a compendium of pooled short hairpin RNA screens on 27 of the same human PDAC cell lines.
A catalog of 710 protein-coding and 46 RNA genes mapping to 20 recurrently gained genomic loci were identified. The gene set was further refined through stringent integration of copy number, gene expression, and RNA interference screening data to uncover 34 candidate driver genes.
Among the candidate genes from the integrative analysis, ECT2 was found to have significantly higher essentiality in specific PDAC cell lines with genomic gains at the 3q26.3 locus, which harbors this gene, suggesting that ECT2 may play an oncogenic role in the PDAC neoplastic process.
本研究通过对拷贝数、基因表达和 RNA 干扰筛选的综合分析，鉴定了胰腺导管腺癌 (PDAC) 中体细胞拷贝数增益所携带的潜在驱动基因。
从公共数据集提取 60 个 PDAC 基因组的体细胞拷贝数增益数据，以鉴定反复出现增益的基因组位点。使用 29 个人 PDAC 细胞系的阵列数据，对在体细胞拷贝数增益中发现的基因集进行拷贝数与基因表达之间的定量关联。对来自 27 个相同人 PDAC 细胞系的汇集短发夹 RNA 筛选的综合分析中评估了相关性最高的基因。
鉴定出了 710 个编码蛋白的基因和 46 个映射到 20 个反复出现增益的基因组位点的 RNA 基因。通过严格整合拷贝数、基因表达和 RNA 干扰筛选数据，进一步对基因集进行了精炼，以揭示 34 个候选驱动基因。
在整合分析的候选基因中，发现 ECT2 在基因组增益位于 3q26.3 位点的特定 PDAC 细胞系中具有更高的重要性，该基因位于该基因座上，这表明 ECT2 可能在 PDAC 肿瘤发生过程中发挥致癌作用。
