The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology.

The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology.
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DOI:
10.1158/0008-5472.can-12-3342
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发表时间:
2013-07-15
期刊:
影响因子:
11.2
通讯作者:
Meltzer PS
Meltzer PS
中科院分区:
医学1区
文献类型:
--
作者:
Abaan OD;Polley EC;Davis SR;Zhu YJ;Bilke S;Walker RL;Pineda M;Gindin Y;Jiang Y;Reinhold WC;Holbeck SL;Simon RM;Doroshow JH;Pommier Y;Meltzer PS

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NCI-60细胞系是癌症研究中最常研究的人类肿瘤细胞系。该小组已经生成了全球最广泛的癌症药理学数据库。此外,这些细胞系已被深入研究,为重点增强我们对肿瘤生物学的理解的假设驱动研究提供了一个独特的平台。在这里,我们报告了通过全外显子组测序(WES)鉴定的NCI-60细胞系中编码变体的全面分析,为社区提供了可能的癌症特异性变体列表。此外,我们鉴定了TP 53、BRAF、ERBB和ATAD 5等基因中的特定变体与nutlin、vemurafenib、厄洛替尼和博来霉素等抗癌药物之间的药物基因组学相关性,证明了数据可用于验证和产生新假设以供进一步研究的多种方式之一。由于新的癌症基因是通过大规模测序研究确定的,这里为NCI-60提供的数据将是一个宝贵的资源,用于识别这些基因突变的细胞系,以进行假设驱动的研究。为了提高数据对更大研究社区的实用性,基因组变异可以以不同的格式从多个来源免费获得,包括CellMiner和Incidity网站。
The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, providing a unique platform for hypothesis driven research focused on enhancing our understanding of tumor biology. Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identified by whole exome sequencing (WES), providing a list of possible cancer specific variants for the community. Furthermore, we identify pharmacogenomic correlations between specific variants in genes like TP53, BRAF, ERBBs and ATAD5 and anti-cancer agents such as nutlin, vemurafenib, erlotinib and bleomycin demonstrating one of many ways the data could be utilized to validate and generate novel hypotheses for further investigation. As new cancer genes are identified through large-scale sequencing studies, the data presented here for the NCI-60 will be an invaluable resource for identifying cell lines with mutations in such genes for hypothesis driven research. To enhance the utility of the data for the greater research community, the genomic variants are freely available in different formats and from multiple sources including the CellMiner and Ingenuity websites.