Discovering functional evolutionary dependencies in human cancers.

Détails

ID Serval
serval:BIB_6F00D45D2EAD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Discovering functional evolutionary dependencies in human cancers.
Périodique
Nature genetics
Auteur(s)
Mina M., Iyer A., Tavernari D., Raynaud F., Ciriello G.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
11/2020
Peer-reviewed
Oui
Volume
52
Numéro
11
Pages
1198-1207
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Cancer cells retain genomic alterations that provide a selective advantage. The prediction and validation of advantageous alterations are major challenges in cancer genomics. Moreover, it is crucial to understand how the coexistence of specific alterations alters response to genetic and therapeutic perturbations. In the present study, we inferred functional alterations and preferentially selected combinations of events in >9,000 human tumors. Using a Bayesian inference framework, we validated computational predictions with high-throughput readouts from genetic and pharmacological screenings on 2,000 cancer cell lines. Mutually exclusive and co-occurring cancer alterations reflected, respectively, functional redundancies able to rescue the phenotype of individual target inhibition, or synergistic interactions, increasing oncogene addiction. Among the top scoring dependencies, co-alteration of the phosphoinositide 3-kinase (PI3K) subunit PIK3CA and the nuclear factor NFE2L2 was a synergistic evolutionary trajectory in squamous cell carcinomas. By integrating computational, experimental and clinical evidence, we provide a framework to study the combinatorial functional effects of cancer genomic alterations.
Pubmed
Création de la notice
05/10/2020 12:54
Dernière modification de la notice
23/11/2020 6:24
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