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Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.
Burdett, Nikki L; Willis, Madelynne O; Alsop, Kathryn; Hunt, Allison L; Pandey, Ahwan; Hamilton, Phineas T; Abulez, Tamara; Liu, Xuan; Hoang, Therese; Craig, Stuart; Fereday, Sian; Hendley, Joy; Garsed, Dale W; Milne, Katy; Kalaria, Shreena; Marshall, Ashley; Hood, Brian L; Wilson, Katlin N; Conrads, Kelly A; Pishas, Kathleen I; Ananda, Sumitra; Scott, Clare L; Antill, Yoland; McNally, Orla; Mileshkin, Linda; Hamilton, Anne; Au-Yeung, George; Devereux, Lisa; Thorne, Heather; Bild, Andrea; Bateman, Nicholas W; Maxwell, G Larry; Chang, Jeffrey T; Conrads, Thomas P; Nelson, Brad H; Bowtell, David D L; Christie, Elizabeth L.
Afiliação
  • Burdett NL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Willis MO; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Alsop K; Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.
  • Hunt AL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Pandey A; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Hamilton PT; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Abulez T; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, Annandale, Victoria, USA.
  • Liu X; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Hoang T; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Craig S; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
  • Fereday S; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Hendley J; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Garsed DW; Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, TX, USA.
  • Milne K; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Kalaria S; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Marshall A; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Hood BL; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Wilson KN; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Conrads KA; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Pishas KI; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Ananda S; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
  • Scott CL; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
  • Antill Y; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
  • McNally O; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Mileshkin L; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Hamilton A; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Au-Yeung G; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Devereux L; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Thorne H; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Bild A; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Bateman NW; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Maxwell GL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Chang JT; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.
  • Conrads TP; Department of Medicine, Western Health, The University of Melbourne, St Albans, Victoria, Australia.
  • Nelson BH; Epworth Healthcare, East Melbourne, Victoria, Australia.
  • Bowtell DDL; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Christie EL; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Nat Genet ; 55(3): 437-450, 2023 03.
Article em En | MEDLINE | ID: mdl-36849657
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenocarcinoma Seroso Limite: Female / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cistadenocarcinoma Seroso Limite: Female / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália