High-grade serous ovarian cancer is usually fatal, however a rare group of patients have exceptional responses and survive >10 years. In the first multi-omic whole genome analysis of long-term survivors we found tumours were more likely to have multiple DNA repair gene alterations, and more frequent alterations overall, resulting in increased predicted neoantigen load, and enhanced immune-response.

Garsed DW, Pandey A, Fereday S, Kennedy CJ, Takahashi K, Alsop K, Hamilton PT, Hendley J, Chiew YE, Traficante N, Provan P, Ariyaratne D, Au-Yeung G, Bateman NW, Bowes L, Brand A, Christie EL, Cunningham JM, Friedlander M, Grout B, Harnett P, Hung J, McCauley B, McNally O, Piskorz AM, Saner FAM, Vierkant RA, Wang C, Winham SJ, Pharoah PDP, Brenton JD, Conrads TP, Maxwell GL, Ramus SJ, Pearce CL, Pike MC, Nelson BH, Goode EL, DeFazio A, Bowtell DDL.

This study was the first analysis of mechanisms underpinning exceptional survival (>10 years) in women with high-grade serous ovarian carcinoma. The results implicated an interaction between faults in DNA repair genes and the immune system in response to treatment. The work provided data that led to the establishment of an international consortium (MOCOG) involving >25 sites in 10 countries to further explore determinants of long-term survival.

Garsed DW, Alsop K, Fereday S, Emmanuel C, Kennedy CJ, Etemadmoghadam D, Gao B, Gebski V, Gares V, Christie EL, Wouters MCA, Milne K, George J, Patch AM, Li J, Arnau GM, Semple T, Gadipally SR, Chiew YE, Hendley J, Mikeska T, Zapparoli GV, Amarasinghe K, Grimmond SM, Pearson JV, Waddell N, Hung J, Stewart CJR, Sharma R, Allan PE, Rambau PF, Traficante N, AOCS Study Group, Group, McNally O, Mileshkin L, Hamilton A, Ananda S, Grossi M, Cohen PA, Leung YC, Rome RM, Beale P, Blomfield P, Friedlander M, Brand A, Dobrovic A, Kobel M, Harnett P, Nelson BH, Bowtell DDL, DeFazio A.

This paper described the integrative analysis of 2,658 whole-cancer genomes across 38 cancer types, providing data to the research community for further interrogation. This paper was part of the unprecedented simultaneous publication of 23 papers, including 6 in Nature.

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium.

A comprehensively review of oncogenic alterations reported in low grade serous ovarian cancer, specifically focussing on actionable alterations and new therapeutic targets in this uncommon subtype of ovarian cancer.

Moujaber T, Balleine RL, Gao B, Madsen I, Harnett PR, DeFazio A.

The results from this study challenged the prevailing view that ovarian cancer patients who relapse within 6 months of the end of treatment should be managed with non-platinum chemotherapy. The results have implications for the design of clinical trials in patients with early relapse.

Lindemann K, Gao B, Mapagu C, Fereday S, Emmanuel C, Alsop K, Traficante N, Australian Ovarian Cancer Study Group Harnett PR, Bowtell DDL, DeFazio A.