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• W2899409885 abstract "Driver mutations in oncogenes encode proteins with gain-of-function properties that enhance fitness. Heterozygous mutations are thus viewed as sufficient for tumorigenesis. We describe widespread oncogenic mutant allele imbalance in 13,448 prospectively characterized cancers. Imbalance was selected for through modest dosage increases of gain-of-fitness mutations. Negative selection targeted haplo-essential effectors of the spliceosome. Loss of the normal allele comprised a distinct class of imbalance driven by competitive fitness, which correlated with enhanced response to targeted therapies. In many cancers, an antecedent oncogenic mutation drove evolutionarily dependent allele-specific imbalance. In other instances, oncogenic mutations co-opted independent copy-number changes via the evolutionary process of exaptation. Oncogenic allele imbalance is a pervasive evolutionary innovation that enhances fitness and modulates sensitivity to targeted therapy." @default.
• W2899409885 created "2018-11-09" @default.
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• W2899409885 date "2018-11-01" @default.
• W2899409885 modified "2023-10-16" @default.
• W2899409885 title "Widespread Selection for Oncogenic Mutant Allele Imbalance in Cancer" @default.
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• W2899409885 doi "https://doi.org/10.1016/j.ccell.2018.10.003" @default.
• W2899409885 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6234065" @default.
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• W2899409885 hasPublicationYear "2018" @default.
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