Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.

Autor:	Burdett NL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia., Willis MO; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Alsop K; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Hunt AL; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, Annandale, Victoria, USA.; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA., Pandey A; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Hamilton PT; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Abulez T; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Liu X; Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, TX, USA., Hoang T; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Craig S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Fereday S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Hendley J; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Garsed DW; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Milne K; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Kalaria S; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Marshall A; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Hood BL; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Wilson KN; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Conrads KA; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Pishas KI; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Ananda S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.; Department of Medicine, Western Health, The University of Melbourne, St Albans, Victoria, Australia.; Epworth Healthcare, East Melbourne, Victoria, Australia., Scott CL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Antill Y; Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.; Cabrini Health, Malvern, Victoria, Australia.; Department of Medical Oncology, Peninsula health, Frankston, Victoria, Australia., McNally O; The Royal Women's Hospital, Parkville, Victoria, Australia.; Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Victoria, Australia., Mileshkin L; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Hamilton A; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; The Royal Women's Hospital, Parkville, Victoria, Australia., Au-Yeung G; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Devereux L; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Thorne H; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Bild A; Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Monrovia, CA, USA., Bateman NW; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, Bethesda, MD, USA., Maxwell GL; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, Annandale, Victoria, USA.; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, Bethesda, MD, USA., Chang JT; Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, TX, USA., Conrads TP; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, Bethesda, MD, USA., Nelson BH; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada., Bowtell DDL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Christie EL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. liz.christie@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. liz.christie@petermac.org.
Jazyk:	angličtina
Zdroj:	Nature genetics [Nat Genet] 2023 Mar; Vol. 55 (3), pp. 437-450. Date of Electronic Publication: 2023 Feb 27.
DOI:	10.1038/s41588-023-01320-2
Abstrakt:	High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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