Essential gene profiles in breast, pancreatic, and ovarian cancer cells.
Essential gene profiles in breast, pancreatic, and ovarian cancer cells.
复制标题
DOI：
10.1158/2159-8290.cd-11-0224
复制
发表时间：
2012-02
期刊：
影响因子：
28.2
通讯作者：
Moffat J
中科院分区：
文献类型：
--
作者：
Marcotte R;Brown KR;Suarez F;Sayad A;Karamboulas K;Krzyzanowski PM;Sircoulomb F;Medrano M;Fedyshyn Y;Koh JLY;van Dyk D;Fedyshyn B;Luhova M;Brito GC;Vizeacoumar FJ;Vizeacoumar FS;Datti A;Kasimer D;Buzina A;Mero P;Misquitta C;Normand J;Haider M;Ketela T;Wrana JL;Rottapel R;Neel BG;Moffat J
基因组分析正在产生大量关于与特定类型癌症相关的多种遗传异常的新信息。对癌症相关遗传异常的全面描述可以提高我们将肿瘤分类为临床相关亚组的能力，有时还可以识别驱动癌症表型的突变基因（“驱动因素”）。然而，更常见的是，癌症相关突变的功能意义很难辨别。全基因组范围内的 shRNA 筛选能够全面鉴定癌细胞生存和增殖所必需的基因，从而提供人类癌症的“功能基因组”图谱来补充基因组研究。使用针对约 16,000 个基因的慢病毒 shRNA 文库和新开发的动态评分方法，我们确定了 72 个乳腺癌、胰腺癌细胞系和卵巢癌细胞系中的必需基因谱。将我们的结果与当前和未来的基因组数据相结合，应该有助于系统地识别这些肿瘤类型的驱动因素、意外的合成致死关系和功能脆弱性。
Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups, and, on occasion, identify mutant genes that drive the cancer phenotype (“drivers”). More often, though, the functional significance of cancer-associated mutations is difficult to discern. Genome-wide pooled shRNA screens enable global identification of the genes essential for cancer cell survival and proliferation, providing a “functional genomic” map of human cancer to complement genomic studies. Using a lentiviral shRNA library targeting ~16,000 genes and a newly developed, dynamic scoring approach, we identified essential gene profiles in 72 breast, pancreatic, and ovarian cancer cell lines. Integrating our results with current and future genomic data should facilitate the systematic identification of drivers, unanticipated synthetic lethal relationships, and functional vulnerabilities of these tumor types.