title: Neomorphic mutations create therapeutic challenges in cancer.
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.
authors.affiliation: Departments of Radiation Oncology and Cancer Biology, University of Cincinnati College of Medicine, UC Barrett Cancer Center, OH, USA.
authors.forename: V
authors.initials: V
authors.lastname: Takiar
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C K M
authors.initials: CK
authors.lastname: Ip
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.
authors.forename: L W T
authors.initials: LW
authors.lastname: Cheung
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D009857:Oncogenes
chemical_list: D014408:Biomarkers, Tumor