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DOI | 10.1038/s41467-019-12039-2 |
The germline genetic component of drug sensitivity in cancer cell lines | |
Menden, Michael P.1,2; Casale, Francesco Paolo2,3; Stephan, Johannes2; Bignell, Graham R.4; Iorio, Francesco2; McDermott, Ultan1,4; Garnett, Mathew J.4; Saez-Rodriguez, Julio2,5,8; Stegle, Oliver2,6,7 | |
2019-09-20 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | England; USA; Germany |
英文摘要 | Patients with seemingly the same tumour can respond very differently to treatment. There are strong, well-established effects of somatic mutations on drug efficacy, but there is atmost anecdotal evidence of a germline component to drug response. Here, we report a systematic survey of how inherited germline variants affect drug susceptibility in cancer cell lines. We develop a joint analysis approach that leverages both germline and somatic variants, before applying it to screening data from 993 cell lines and 265 drugs. Surprisingly, we find that the germline contribution to variation in drug susceptibility can be as large or larger than effects due to somatic mutations. Several of the associations identified have a direct relationship to the drug target. Finally, using 17-AAG response as an example, we show how germline effects in combination with transcriptomic data can be leveraged for improved patient stratification and to identify new markers for drug sensitivity. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000442521500010 |
WOS关键词 | GENOME-WIDE ASSOCIATION ; OXIDOREDUCTASE 1 ; OVARIAN-CANCER ; DT-DIAPHORASE ; POLYMORPHISM ; RESISTANCE ; MUTATIONS ; THERAPY ; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN ; EXPRESSION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204551 |
专题 | 资源环境科学 |
作者单位 | 1.AstraZeneca, Oncol Innovat Med & Early Drug Dev, Milton Sci Pk, Cambridge CB4 0FZ, England; 2.European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England; 3.Microsoft Res New England, Cambridge, MA 02142 USA; 4.Wellcome Trust Sanger Inst, Genome Campus, Cambridge CB10 1SD, England; 5.RWTH Aachen Univ Hosp, Joint Res Ctr Computat Biomed JRC Combine, D-52074 Aachen, Germany; 6.European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany; 7.German Canc Res Ctr, Div Computat Genom & Syst Genet, D-69120 Heidelberg, Germany; 8.Heidelberg Univ, Inst Computat Biomed, Fac Med, D-69120 Heidelberg, Germany |
推荐引用方式 GB/T 7714 | Menden, Michael P.,Casale, Francesco Paolo,Stephan, Johannes,et al. The germline genetic component of drug sensitivity in cancer cell lines[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Menden, Michael P..,Casale, Francesco Paolo.,Stephan, Johannes.,Bignell, Graham R..,Iorio, Francesco.,...&Stegle, Oliver.(2019).The germline genetic component of drug sensitivity in cancer cell lines.NATURE COMMUNICATIONS,9. |
MLA | Menden, Michael P.,et al."The germline genetic component of drug sensitivity in cancer cell lines".NATURE COMMUNICATIONS 9(2019). |
条目包含的文件 | 条目无相关文件。 |
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