A Landscape of Pharmacogenomic Interactions in Cancer

Title

A Landscape of Pharmacogenomic Interactions in Cancer

 Author

Iorio, Francesco (European Molecular Biology Laboratory; Wellcome Trust Sanger Institute)
Knijnenburg, Theo A. (Institute for Systems Biology)
Vis, Daniel J. (Netherlands Cancer Institute)
Bignell, Graham R. (Wellcome Trust Sanger Institute)
Menden, Michael P. (European Molecular Biology Laboratory; Rheinisch-Westfälische Technische Hochschule)
Schubert, Michael (European Molecular Biology Laboratory)
Aben, N.N. (TU Delft Pattern Recognition and Bioinformatics)
Gonçalves, Emanuel (European Molecular Biology Laboratory)
Barthorpe, Syd (Wellcome Trust Sanger Institute)
Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics) ORCID 0000-0002-1656-6995

 Date

2016

 Abstract

Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancerdriven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully
recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance
of tissue lineage in mediating drug response. Logicbased modeling uncovers combinations of alterations that sensitize to drugs, while machine learning
demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.

 To reference this document use:

http://resolver.tudelft.nl/uuid:0c522d40-cf3e-438c-bc07-fcf708095ad0

 DOI

https://doi.org/10.1016/j.cell.2016.06.017

 ISSN

0092-8674

 Source

Cell, 166 (3), 740-754

 Part of collection

Institutional Repository

 Document type

journal article

 Rights

© 2016 Francesco Iorio, Theo A. Knijnenburg, Daniel J. Vis, Graham R. Bignell, Michael P. Menden, Michael Schubert, N.N. Aben, Emanuel Gonçalves, Syd Barthorpe, L.F.A. Wessels, More Authors
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