Journal article
EIF1AX and NRAS mutations co-occur and cooperate in low-grade serous ovarian carcinomas
D Etemadmoghadam, WJ Azar, Y Lei, T Moujaber, DW Garsed, CJ Kennedy, S Fereday, C Mitchell, YE Chiew, J Hendley, R Sharma, PR Harnett, J Li, EL Christie, AM Patch, J George, G Au-Yeung, GM Arnau, TP Holloway, T Semple Show all
Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2017
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 LG..
View full abstractRelated Projects (3)
Grants
Awarded by Medical Research and Materiel Command
Funding Acknowledgements
This work was supported by Cancer Council New South Wales (RG-15-23), The National Health and Medical Research Council of Australia (NHMRCID631701), Worldwide Cancer Research (09-0676), and Cancer Australia (1004673). The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania, and the National Health and Medical Research Council of Australia (NHMRC; ID400413, ID400281). The AOCS gratefully acknowledges additional support from S. Boldeman, the Agar family, Ovarian Cancer Australia and Ovarian Cancer Action (UK). The Gynaecological Oncology at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was supported by grants from the NHMRC (ID310670 and ID628903) and the Cancer Institute New South Wales (12/RIG/1-17 and 15/RIG/1-16). A. de Fazio is supported by the University of Sydney Cancer Research Fund and Cancer Institute NSW, through the Sydney West Translational Cancer Research Centre. T. Moujaber is a recipient of a Westmead Medical Research Foundation PhD Scholarship.