Title

EIF1AX and NRAS Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas.

Document Type

Article

Publication Date

8-15-2017

Keywords

Cell Line, Tumor, Cystadenocarcinoma, Serous, Eukaryotic Initiation Factor-1, Female, GTP Phosphohydrolases, Gene Knockdown Techniques, Humans, Membrane Proteins, Mutagenesis, Site-Directed, Mutation, Neoplasm Grading, Neoplasm Staging, Ovarian Neoplasms

JAX Source

Cancer Res 2017 Aug 15; 77(16):4268-4278

PMID

28646021

DOI

https://doi.org/10.1158/0008-5472.CAN-16-2224

Abstract

Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing, we identified recurrent mutations in the protein translational regulator EIF1AX and in NF1, USP9X, KRAS, BRAF, and NRAS RAS pathway mutations were mutually exclusive; however, we found significant co-occurrence of mutations in NRAS and EIF1AX Missense EIF1AX mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity. Coexpression of mutant NRAS and EIF1AX proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer. Cancer Res; 77(16); 4268-78. ©2017 AACR.