The germline genetic component of drug sensitivity in cancer cell lines
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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 August 2018
|
| In: |
Nature Communications
Year: 2018, Jahrgang: 9 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-05811-3 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-018-05811-3
|
| Verfasserangaben: | Michael P. Menden, Francesco Paolo Casale, Johannes Stephan, Graham R. Bignell, Francesco Iorio, Ultan McDermott, Mathew J. Garnett, Julio Saez-Rodriguez & Oliver Stegle |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1693488450 | ||
| 003 | DE-627 | ||
| 005 | 20241223012020.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200330s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-018-05811-3 |2 doi | |
| 035 | |a (DE-627)1693488450 | ||
| 035 | |a (DE-599)KXP1693488450 | ||
| 035 | |a (OCoLC)1341311295 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Menden, Michael |e VerfasserIn |0 (DE-588)1203168314 |0 (DE-627)1687989591 |4 aut | |
| 245 | 1 | 4 | |a The germline genetic component of drug sensitivity in cancer cell lines |c Michael P. Menden, Francesco Paolo Casale, Johannes Stephan, Graham R. Bignell, Francesco Iorio, Ultan McDermott, Mathew J. Garnett, Julio Saez-Rodriguez & Oliver Stegle |
| 264 | 1 | |c 23 August 2018 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 30.03.2020 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Benzoquinones | |
| 650 | 4 | |a Cell Line, Tumor | |
| 650 | 4 | |a Drug Screening Assays, Antitumor | |
| 650 | 4 | |a Germ Cells | |
| 650 | 4 | |a Germ-Line Mutation | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Lactams, Macrocyclic | |
| 650 | 4 | |a Neoplasms | |
| 650 | 4 | |a Quantitative Trait Loci | |
| 700 | 1 | |a Casale, Francesco Paolo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stephan, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bignell, Graham R. |e VerfasserIn |4 aut | |
| 700 | 1 | |8 1\p |a Iorio, Francesco |e VerfasserIn |0 (DE-588)1171361106 |0 (DE-627)104050583X |0 (DE-576)513711198 |4 aut | |
| 700 | 1 | |a McDermott, Ultan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garnett, Mathew J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sáez Rodríguez, Julio |d 1978- |e VerfasserIn |0 (DE-588)133764362 |0 (DE-627)555766632 |0 (DE-576)300083114 |4 aut | |
| 700 | 1 | |a Stegle, Oliver |e VerfasserIn |0 (DE-588)1198235063 |0 (DE-627)1680553755 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature Communications |d [London] : Springer Nature, 2010 |g 9(2018) Artikel-Nummer 3385, 8 Seiten |h Online-Ressource |w (DE-627)626457688 |w (DE-600)2553671-0 |w (DE-576)331555905 |x 2041-1723 |7 nnas |a The germline genetic component of drug sensitivity in cancer cell lines |
| 773 | 1 | 8 | |g volume:9 |g year:2018 |g extent:8 |a The germline genetic component of drug sensitivity in cancer cell lines |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41467-018-05811-3 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20200330 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 1198235063 |a Stegle, Oliver |m 1198235063:Stegle, Oliver |d 140000 |e 140000PS1198235063 |k 0/140000/ |p 9 |y j | ||
| 998 | |g 133764362 |a Sáez Rodríguez, Julio |m 133764362:Sáez Rodríguez, Julio |d 910000 |d 912900 |d 700000 |d 716000 |e 910000PS133764362 |e 912900PS133764362 |e 700000PS133764362 |e 716000PS133764362 |k 0/910000/ |k 1/910000/912900/ |k 0/700000/ |k 1/700000/716000/ |p 8 | ||
| 999 | |a KXP-PPN1693488450 |e 3615694961 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"physDesc":[{"extent":"8 S."}],"id":{"eki":["1693488450"],"doi":["10.1038/s41467-018-05811-3"]},"recId":"1693488450","name":{"displayForm":["Michael P. Menden, Francesco Paolo Casale, Johannes Stephan, Graham R. Bignell, Francesco Iorio, Ultan McDermott, Mathew J. Garnett, Julio Saez-Rodriguez & Oliver Stegle"]},"origin":[{"dateIssuedDisp":"23 August 2018","dateIssuedKey":"2018"}],"title":[{"title_sort":"germline genetic component of drug sensitivity in cancer cell lines","title":"The germline genetic component of drug sensitivity in cancer cell lines"}],"note":["Gesehen am 30.03.2020"],"person":[{"role":"aut","roleDisplay":"VerfasserIn","given":"Michael","family":"Menden","display":"Menden, Michael"},{"given":"Francesco Paolo","roleDisplay":"VerfasserIn","role":"aut","display":"Casale, Francesco Paolo","family":"Casale"},{"given":"Johannes","roleDisplay":"VerfasserIn","role":"aut","display":"Stephan, Johannes","family":"Stephan"},{"display":"Bignell, Graham R.","family":"Bignell","given":"Graham R.","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Iorio, Francesco","family":"Iorio","given":"Francesco","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Ultan","family":"McDermott","display":"McDermott, Ultan"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Mathew J.","family":"Garnett","display":"Garnett, Mathew J."},{"display":"Sáez Rodríguez, Julio","family":"Sáez Rodríguez","given":"Julio","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Stegle, Oliver","family":"Stegle","given":"Oliver","role":"aut","roleDisplay":"VerfasserIn"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"relHost":[{"disp":"The germline genetic component of drug sensitivity in cancer cell linesNature Communications","language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["626457688"],"zdb":["2553671-0"],"issn":["2041-1723"]},"type":{"media":"Online-Ressource","bibl":"periodical"},"recId":"626457688","pubHistory":["2010-"],"part":{"volume":"9","text":"9(2018) Artikel-Nummer 3385, 8 Seiten","year":"2018","extent":"8"},"origin":[{"publisher":"Springer Nature ; Nature Publishing Group UK","dateIssuedDisp":"[2010]-","publisherPlace":"[London] ; [London]"}],"title":[{"title":"Nature Communications","title_sort":"Nature Communications"}],"note":["Gesehen am 13.06.24"]}]} | ||
| SRT | |a MENDENMICHGERMLINEGE2320 | ||