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
Volume
77
Issue
16
First Page
4268
Last Page
4278
ISSN
1538-7445
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.
Recommended Citation
Etemadmoghadam D,
Azar W,
Lei Y,
Moujaber T,
Garsed D,
Kennedy C,
Fereday S,
Mitchell C,
Chiew Y,
Hendley J,
Sharma R,
Harnett P,
Li J,
Christie E,
Patch A,
George J,
Au-Yeung G,
Mir Arnau G,
Holloway T,
Semple T,
Pearson J,
Waddell N,
Grimmond S,
Köbel M,
Rizos H,
Lomakin I,
Bowtell D,
deFazio A.
EIF1AX and NRAS Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas. Cancer Res 2017 Aug 15; 77(16):4268-4278