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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Homologous recombination DNA repair pathway disruption and retinoblastoma protein loss are associated with exceptional survival in high-grade serous ovarian cancer
Clinical Cancer Research, Volume 24, No. 3, Year 2018
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Description
Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths. Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing. Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8þ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival. Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. © 2017 American Association for Cancer Research.
Authors & Co-Authors
Alsop, Kathryn
Australia, Melbourne
Peter Maccallum Cancer Centre
Fereday, Sian
Australia, Melbourne
Peter Maccallum Cancer Centre
Kennedy, Catherine J.
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Etemadmoghadam, Dariush
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
University of Melbourne
Gao, Bo
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Patch, Ann Marie
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Li, Jason Ying Ki
Australia, Melbourne
Peter Maccallum Cancer Centre
Chiew, Yoke Eng
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Hendley, Joy
Australia, Melbourne
Peter Maccallum Cancer Centre
Grimmond, Sean M.
Australia, Melbourne
University of Melbourne
Hung, Jillian A.
Australia, Sydney
Westmead Hospital
Stewart, Colin J.R.
Australia, Perth
King Edward Memorial Hospital for Women
Sharma, Raghwa N.
Australia, Sydney
Westmead Hospital
Australia, Sydney
The University of Sydney
Rambau, Peter Fabian
Canada, Calgary
University of Calgary
Traficante, Nadia
Unknown Affiliation
McNally, Orla M.
Australia, Melbourne
University of Melbourne
Australia, Melbourne
Royal Women's Hospital, Carlton
Mileshkin, Linda Rose
Australia, Melbourne
Peter Maccallum Cancer Centre
Hamilton, Anne L.
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
Royal Women's Hospital, Carlton
Australia, Melbourne
University of Melbourne
Ananda, Sumitra S.
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
Royal Women's Hospital, Carlton
Cohen, Paul A.
Australia, Perth
St John of God Health Care
Australia, Fremantle
The University of Notre Dame Australia
Australia, Perth
The University of Western Australia
Leung, Yee Chit
Australia, Perth
The University of Western Australia
Friedlander, M. L.
Australia, Sydney
Unsw Sydney
Dobrovic, Alexander N.
Australia, Melbourne
Olivia Newton-john Cancer Research Institute
Australia, Melbourne
La Trobe University
Australia, Melbourne
University of Melbourne
Köbel, Martin
Canada, Calgary
University of Calgary
Harnett, Paul R.
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Australia, Sydney
The University of Sydney
Bowtell, David D.L.
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
University of Melbourne
Australia, Sydney
The Kinghorn Cancer Centre
DeFazio, Anna
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Australia, Sydney
The University of Sydney
Statistics
Citations: 59
Authors: 27
Affiliations: 21
Identifiers
Doi:
10.1158/1078-0432.CCR-17-1621
ISSN:
10780432
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Design
Cross Sectional Study
Participants Gender
Female