Neomorphic mutations create therapeutic challenges in cancer

V. Takiar, C. K.M. Ip, M. Gao, Gordon 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
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Takiar, V., Ip, C. K. M., Gao, M., Mills, G., & 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