Journal article

Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver

Catherine Emmanuel, Yoke-Eng Chiew, Joshy George, Dariush Etemadmoghadam, Michael S Anglesio, Raghwa Sharma, Peter Russell, Catherine Kennedy, Sian Fereday, Jillian Hung, Laura Galletta, Russell Hogg, Gerard V Wain, Alison Brand, Rosemary Balleine, Laura MacConaill, Emanuele Palescandolo, Sally M Hunter, Ian Campbell, Alexander Dobrovic Show all



PURPOSE: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. EXPERIMENTAL DESIGN: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent bord..

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Awarded by U.S. Army Medical Research and Materiel Command

Funding Acknowledgements

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 CouncilNew 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 Gynaecological Oncology Biobank at Westmead is funded by Cancer Institute NSW and is amember bank of the Australasian Biospecimens Network-Oncology, funded byNHMRC(ID310670, ID628903). A. de Fazio is funded by the University of Sydney Cancer Research Fund, and A. de Fazio and P. R. Harnett are funded by the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. This work was also supported by a grant from the Cancer Council of New South Wales (CCNSW RG10-05). This work was also supported by the Victorian Breast Cancer Research Consortium (VBCRC), the NHMRC (ID 628630), Cancer Australia (1004673), and theEmer Casey Foundation. H. Do was funded by a fellowship from the Cancer Council of Victoria, and S. Q. Wong was supported by the Melbourne Melanoma Project, funded by the Victorian Cancer Agency Translational Research Program. L. MacConaill and E. Palescandolo were funded by the Dana-Farber Cancer Institute.