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Functional genomics to explore cancer cell vulnerabilities

机译：探索癌细胞脆弱性的功能基因组学

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Our understanding of glioblastoma multiforme (GBM), the most common form of primary brain cancer, has been significantly advanced by recent efforts to characterize the cancer genome using unbiased high-throughput sequencing analyses. While these studies have documented hundreds of mutations, gene copy alterations, and chromosomal abnormalities, only a subset of these alterations are likely to impact tumor initiation or maintenance. Furthermore, genes that are not altered at the genomic level may play essential roles in tumor initiation and maintenance. Identification of these genes is critical for therapeutic development and investigative methodologies that afford insight into biological function. This requirement has largely been fulfilled with the emergence of RNA interference (RNAi) and high-throughput screening technology. In this article, the authors discuss the application of genome-wide, highthroughput RNAi-based genetic screening as a powerful tool for the rapid and cost-effective identification of genes essential for cancer proliferation and survival. They describe how these technologies have been used to identify genes that are themselves selectively lethal to cancer cells, or synthetically lethal with other oncogenic mutations. The article is intended to provide a platform for how RNAi libraries might contribute to uncovering glioma cell vulnerabilities and provide information that is highly complementary to the structural characterization of the glioblastoma genome. The authors emphasize that unbiased, systems-level structural and functional genetic approaches are complementary efforts that should facilitate the identification of genes involved in the pathogenesis of GBM and permit the identification of novel drug targets.
机译：最近，我们通过使用无偏高通量测序分析来表征癌症基因组的努力，已经大大提高了我们对成胶质母细胞瘤（GBM）（最常见的原发性脑癌）的认识。尽管这些研究已记录了数百种突变，基因拷贝改变和染色体异常，但这些改变中只有一部分可能影响肿瘤的发生或维持。此外，在基因组水平上未改变的基因可能在肿瘤的起始和维持中起重要作用。这些基因的鉴定对于提供生物学功能见解的治疗开发和研究方法至关重要。 RNA干扰（RNAi）和高通量筛选技术的出现已基本满足了这一要求。在本文中，作者讨论了基于全基因组，高通量RNAi的遗传筛选作为快速，经济高效地鉴定对于癌症扩散和存活至关重要的基因的强大工具的应用。他们描述了如何使用这些技术来鉴定对癌细胞有选择性致死或与其他致癌突变合成致死的基因。本文旨在为RNAi文库如何有助于发现神经胶质瘤细胞漏洞提供一个平台，并提供与胶质母细胞瘤基因组的结构表征高度互补的信息。作者强调，无偏见，系统级的结构和功能遗传方法是互补的工作，应有助于鉴定涉及GBM发病机理的基因并允许鉴定新的药物靶标。

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