Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities

Dane Cheasley; Abhimanyu Nigam; Magnus Zethoven; Sally Hunter; Dariush Etemadmoghadam; Timothy Semple; Prue Allan; Mark S Carey; Marta L Fernandez; Amy Dawson; Martin Kobel; David G Huntsman; Cecile Le Page; Anne-Marie Mes-Masson; Diane Provencher; Neville Hacker; Yunkai Gao; David Bowtell; Anna deFazio; Kylie L Gorringe; Ian G Campbell

Journal article

Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities

Dane Cheasley, Abhimanyu Nigam, Magnus Zethoven, Sally Hunter, Dariush Etemadmoghadam, Timothy Semple, Prue Allan, Mark S Carey, Marta L Fernandez, Amy Dawson, Martin Kobel, David G Huntsman, Cecile Le Page, Anne-Marie Mes-Masson, Diane Provencher, Neville Hacker, Yunkai Gao, David Bowtell, Anna deFazio, Kylie L Gorringe Show all

JOURNAL OF PATHOLOGY | WILEY | Published : 2020

DOI: 10.1002/path.5545

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Abstract

Low-grade serous ovarian carcinoma (LGSOC) is associated with a poor response to existing chemotherapy, highlighting the need to perform comprehensive genomic analysis and identify new therapeutic vulnerabilities. The data presented here represent the largest genetic study of LGSOCs to date (n = 71), analysing 127 candidate genes derived from whole exome sequencing cohorts to generate mutation and copy-number variation data. Additionally, immunohistochemistry was performed on our LGSOC cohort assessing oestrogen receptor, progesterone receptor, TP53, and CDKN2A status. Targeted sequencing identified 47% of cases with mutations in key RAS/RAF pathway genes (KRAS, BRAF, and NRAS), as well as m..

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University of Melbourne Researchers

Kylie Gorringe Author The Sir Peter Maccallum Department of Oncology

Dane Cheasley Author The Sir Peter Maccallum Department of Oncology

David Bowtell Author The Sir Peter Maccallum Department of Oncology

Ian Campbell Author The Sir Peter Maccallum Department of Oncology

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Awarded by Cancer Australia

Awarded by Terry Fox Research Institute

Awarded by US Army Medical Research and Materiel Command

Awarded by NHMRC

Funding Acknowledgements

This work was supported by the Australian Gynaecological Cancer Foundation and Way In Network (TP825458, held by DC), the National Health and Medical Research Council (APP1092856 and APP1041975, held by IC), Cancer Australia (APP1142697, held by AdeF, KG, and DE), and the Terry Fox Research Institute (#2009-15). The Australian Ovarian Cancer Study was supported by the US 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 NHMRC (ID400413 and ID400281). The Australian Ovarian Cancer Study gratefully acknowledges additional support from S Boldeman, The Agar family, Ovarian Cancer Australia, and Ovarian Cancer Action. The funders had no role in the design and execution of this study.