Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies

Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies a...

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Bibliographic Details
Published in:Cancer cell 2017-08, Vol.32 (2), p.155-168.e6
Main Authors: Mina, Marco, Raynaud, Franck, Tavernari, Daniele, Battistello, Elena, Sungalee, Stephanie, Saghafinia, Sadegh, Laessle, Titouan, Sanchez-Vega, Francisco, Schultz, Nikolaus, Oricchio, Elisa, Ciriello, Giovanni
Format: Article
Language:English
Subjects:
Algorithms
cancer evolution
Carcinogenesis
conditional selection
Evolution, Molecular
Gene Expression Profiling
Genomics
Humans
interdependent therapeutic response
Models, Genetic
Neoplasms - genetics
oncogenic dependencies
selected events
Selection, Genetic
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Summary:Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. [Display omitted] •SELECT identifies cancer evolutionary dependencies from alteration occurrences•Pan-cancer dependencies reflect tissue-independent functional interactions•Pan-cancer dependencies influence response to therapy•Conditional selection is required for the emergence of evolutionary dependencies Using an algorithmic approach that they design, Mina et al. construct a pan-cancer map of oncogenic dependencies and find several co-dependent alterations that modify drug response. These results provide a framework to improve cancer therapy by anticipating drug resistance and proposing alternative strategies.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccell.2017.06.010