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Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants.

Cell Rep. 2016; 
Brenan L, Andreev A, Cohen O, Pantel S, Kamburov A, Cacchiarelli D, Persky NS, Zhu C, Bagul M, Goetz EM, Burgin AB, Garraway LA, Getz G, Mikkelsen TS, Piccioni F, Root DE, Johannessen CM.
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Mutagenesis Services 4) was synthesized (GenScript), and site-directed mutagenesis was performed in pDONOR223 to all reported ERK2 mutants. Get A Quote

摘要

Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants. Gain-of-function ERK2 mutants induced... More

关键词

ERK; MAPK; cancer; functional biology; precision medicine; precision oncology; rare mutants