American Association for Cancer Research
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Supplemental Materials and Methods from EIF1AX and NRAS Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas

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posted on 2023-03-31, 00:44 authored by Dariush Etemadmoghadam, Walid J. Azar, Ying Lei, Tania Moujaber, Dale W. Garsed, Catherine J. Kennedy, Sian Fereday, Chris Mitchell, Yoke-Eng Chiew, Joy Hendley, Raghwa Sharma, Paul R. Harnett, Jason Li, Elizabeth L. Christie, Ann-Marie Patch, Joshy George, George Au-Yeung, Gisela Mir Arnau, Timothy P. Holloway, Timothy Semple, John V. Pearson, Nicola Waddell, Sean M. Grimmond, Martin Köbel, Helen Rizos, Ivan B. Lomakin, David D.L. Bowtell, Anna deFazio

Supplemental materials and methods

Funding

Cancer Council New South Wales

NHMRC

Worldwide Cancer Research

Cancer Australia

U.S. Army Medical Research and Materiel Command

Cancer Council Victoria

Queensland Cancer

Cancer Council South Australia

Cancer Foundation of Western Australia

Cancer Council Tasmania

AOCS

Cancer Institute New South Wales

University of Sydney Cancer Research

Cancer Institute NSW

Westmead Medical Research Foundation

History

ARTICLE 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.

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