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A Landscape of Pharmacogenomic Interactions in Cancer.

Cell | 2016

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 cancer-driven 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. Logic-based 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.

Pubmed ID: 27397505 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 102696
  • Agency: NCI NIH HHS, United States
    Id: U24 CA143835
  • Agency: Marie Curie, United Kingdom
  • Agency: European Research Council, International
    Id: 268626
  • Agency: Wellcome Trust, United Kingdom
    Id: 086375
  • Agency: Cancer Research UK, United Kingdom
  • Agency: Wellcome Trust, United Kingdom

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This is a list of tools and resources that we have found mentioned in this publication.


Genomics of Drug Sensitivity in Cancer (tool)

RRID:SCR_011956

A genomics database project is an academic research program to identify molecular features of cancers that predict response to anti-cancer drugs.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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COSMIC - Catalogue Of Somatic Mutations In Cancer (tool)

RRID:SCR_002260

Database to store and display somatic mutation information and related details and contains information relating to human cancers. The mutation data and associated information is extracted from the primary literature. In order to provide a consistent view of the data a histology and tissue ontology has been created and all mutations are mapped to a single version of each gene. The data can be queried by tissue, histology or gene and displayed as a graph, as a table or exported in various formats.
Some key features of COSMIC are:
* Contains information on publications, samples and mutations. Includes samples which have been found to be negative for mutations during screening therefore enabling frequency data to be calculated for mutations in different genes in different cancer types.
* Samples entered include benign neoplasms and other benign proliferations, in situ and invasive tumours, recurrences, metastases and cancer cell lines.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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minfi (tool)

RRID:SCR_012830

Software tools for analyzing and visualizing Illumina''s 450k array data.

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