Highlight talk – Theme: Genes
Abstract
Systematic studies of cancer genomes are providing 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 cancer-driving alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation and gene expression) can be mapped to 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic aberrations identified in tumors, that many of these associate with drug response, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of aberrations 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.
Authors
Francesco Iorio, EBI, United Kingdom
Theo Knijnenburg, ISB, United States
Daniel Vis, NKI, Netherlands
Graham Bignell, WTSI, United Kingdom
Michael Menden, EBI, United Kingdom
Nanne Aben, NKI, Netherlands
Lodewyk Wessels, NKI-AVL, Netherlands
Julio Saez-Rodriguez, Aachen University, Germany
Ultan McDermott, WTSI, United Kingdom
Mathew Garnett, WTSI, United Kingdom
Source of publication
Cell, 2016, To appear