Neomorphic mutations create therapeutic challenges in cancer

V. Takiar, C. K.M. Ip, M. Gao, G. B. Mills, L. W.T. Cheung

    Research output: Contribution to journalReview article

    14 Scopus citations

    Abstract

    Oncogenesis is a pathologic process driven by genomic aberrations, including changes in nucleotide sequences. The majority of these mutational events fall into two broad categories: inactivation of tumor suppressor genes (hypomorph, antimorph or amorph) or activation of oncogenes (hypermorph). The recent surge in genome sequence data and functional genomics research has ushered in the discovery of aberrations in a third category: gain-of-novel-function mutation (neomorph). These neomorphic mutations, which can be found in both tumor suppressor genes and oncogenes, produce proteins with entirely different functions from their respective wild-type (WT) proteins and the other morphs. The unanticipated phenotypic outcomes elicited by neomorphic mutations imply that tumors with the neomorphic mutations may not respond to therapies designed to target the WT protein. Therefore, understanding the functional activities of each genomic aberration to be targeted is crucial in devising effective treatment strategies that will benefit specific cancer patients.

    Original languageEnglish (US)
    Pages (from-to)1607-1618
    Number of pages12
    JournalOncogene
    Volume36
    Issue number12
    DOIs
    StatePublished - Mar 23 2017

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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  • Cite this

    Takiar, V., Ip, C. K. M., Gao, M., Mills, G. B., & Cheung, L. W. T. (2017). Neomorphic mutations create therapeutic challenges in cancer. Oncogene, 36(12), 1607-1618. https://doi.org/10.1038/onc.2016.312