| Literature DB >> 28646021 |
Dariush Etemadmoghadam1,2,3, Walid J Azar1, Ying Lei4,5,6, Tania Moujaber4,5,6,7, Dale W Garsed1,2, Catherine J Kennedy4,5, Sian Fereday1, Chris Mitchell1, Yoke-Eng Chiew4,5, Joy Hendley1, Raghwa Sharma6,8,9, Paul R Harnett4,6,7, Jason Li1, Elizabeth L Christie1, Ann-Marie Patch10, Joshy George11, George Au-Yeung1, Gisela Mir Arnau1, Timothy P Holloway1, Timothy Semple1, John V Pearson10, Nicola Waddell10, Sean M Grimmond12, Martin Köbel13, Helen Rizos14, Ivan B Lomakin15, David D L Bowtell16,2,3,17,18, Anna deFazio19,5,6.
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. ©2017 American Association for Cancer Research.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28646021 DOI： 10.1158/0008-5472.CAN-16-2224
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701