Author
Listed:
- Michael P. Menden
(AstraZeneca
European Bioinformatics Institute (EMBL-EBI))
- Francesco Paolo Casale
(European Bioinformatics Institute (EMBL-EBI)
Microsoft Research New England)
- Johannes Stephan
(European Bioinformatics Institute (EMBL-EBI))
- Graham R. Bignell
(Wellcome Trust Sanger Institute)
- Francesco Iorio
(European Bioinformatics Institute (EMBL-EBI))
- Ultan McDermott
(AstraZeneca
Wellcome Trust Sanger Institute)
- Mathew J. Garnett
(Wellcome Trust Sanger Institute)
- Julio Saez-Rodriguez
(European Bioinformatics Institute (EMBL-EBI)
Joint Research Center for Computational Biomedicine (JRC-Combine)
Heidelberg University)
- Oliver Stegle
(European Bioinformatics Institute (EMBL-EBI)
Genome Biology Unit
German Cancer Research Center (DKFZ))
Abstract
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 at-most 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.
Suggested Citation
Michael P. Menden & Francesco Paolo Casale & Johannes Stephan & Graham R. Bignell & Francesco Iorio & Ultan McDermott & Mathew J. Garnett & Julio Saez-Rodriguez & Oliver Stegle, 2018.
"The germline genetic component of drug sensitivity in cancer cell lines,"
Nature Communications, Nature, vol. 9(1), pages 1-8, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05811-3
DOI: 10.1038/s41467-018-05811-3
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05811-3. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.