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https://repository.monashhealth.org/monashhealthjspui/handle/1/37301| Title: | Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma. | Authors: | Jones M.;Ferguson K.;Martin K.;Martyn A.;Ranieri B.;White J.;Jayde V.;Mamers P.;Bowes L.;Giles D.;Hendley J.;Schmidt T.;Shirley H.;Ball C.;Young C.;Viduka S.;Tran H. ;Bilic S.;Glavinas L.;Brooks J.;Stuart-Harris R.;Kirsten F.;Rutovitz J.;Brand A.;Byth K.;Jaworski R.;Harnett P.;Sharma R.;Wain G.;Ward B.;Papadimos D.;Crandon A.;Cummings M.;Horwood K.;Obermair A.;Perrin L.;Wyld D.;Nicklin J.;Davy M.;Oehler M.K.;Hall C.;Dodd T.;Healy T.;Pittman K.;Henderson D.;Miller J.;Pierdes J.;Blomfield P.;Challis D.;McIntosh R.;Parker A.;Brown B.;Rome R.;Allen D.;Grant P.;Hyde S.;Laurie R.;Robbie M.;Healy D.;Manolitsas T.;McNealage J.;Rogers P.;Susil B.;Sumithran E.;Simpson I.;Phillips K.;Rischin D.;Fox S.;Johnson D.;Lade S.;Loughrey M.;O'Callaghan N.;Murray W.;Waring P.;Billson V.;Pyman J.;Neesham D.;Quinn M.;Underhill C.;Ng L.F.;Blum R.;Ganju V.;Hammond I.;Leung Y.;McCartney A. ;Buck M.;Haviv I.;Purdie D.;Whiteman D.;Zeps N.;deFazio A.;McNeish I.A.;Bowtell D.D.;Swisher E.M.;Dobrovic A.;Wakefield M.J.;Scott C.L.;Bell R. ;Jobling T. ;Kondrashova O.;Topp M.;Nesic K.;Lieschke E.;Ho G.-Y.;Harrell M.I.;Zapparoli G.V.;Hadley A.;Holian R.;Boehm E.;Heong V.;Sanij E.;Pearson R.B.;Krais J.J.;Johnson N.;McNally O.;Ananda S.;Alsop K.;Hutt K.J.;Kaufmann S.H.;Lin K.K.;Harding T.C.;Traficante N.;Chenevix-Trench G.;Green A.;Webb P.;Gertig D.;Fereday S.;Moore S.;Hung J.;Harrap K.;Sadkowsky T.;Pandeya N.;Malt M.;Mellon A.;Robertson R.;VandenBergh T.;Mackenzie P.;Maidens J.;Nattress K.;Chiew Y.E.;Stenlake A.;Sullivan H.;Alexander B.;Ashover P.;Brown S.;Corrish T.;Green L.;Jackman L.;Galletta L.;Clingan P.;Glasgow A.;Proietto A.;Braye S.;Otton G.;Shannon J.;Bonaventura T.;Stewart J.;Begbie S.;Friedlander M.;Bell D.;Baron-Hay S.;Ferrier A.;Gard G.;Nevell D.;Pavlakis N.;Valmadre S.;Young B.;Camaris C.;Crouch R.;Edwards L.;Hacker N.;Marsden D.;Robertson G.;Beale P.;Beith J.;Carter J.;Dalrymple C.;Houghton R.;Russell P.;Links M.;Grygiel J.;Hill J. | Institution: | (Kondrashova, Topp, Nesic, Lieschke, Ho, Hadley, Holian, Boehm, Heong, Wakefield, Scott) The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Kondrashova, Nesic, Ho, Hadley, Heong) Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia (Topp, Hutt, Scott) Department of Medicine and Health Sciences, Monash University, Clayton, VIC 3168, Australia (Ho, Heong, McNally, Ananda, Billson, Pyman, Neesham, Quinn) Royal Women's Hospital, Parkville, VIC 3052, Australia (Ho, Sanij, Pearson, Alsop, Traficante, Bowtell, Scott) Research Division, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC 3010, Australia (Harrell, Swisher) Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, United States (Zapparoli, Dobrovic) Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia (Zapparoli, Dobrovic) School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia (Holian, Boehm) School of Medicine, University of Melbourne, Parkville, VIC 3052, Australia (Sanij, Traficante, Bowtell, Dobrovic) Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3010, Australia (Pearson) Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3010, Australia (Pearson) Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia (Pearson) Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia (Krais, Johnson) Fox Chase Cancer Centre, Philadelphia, PA 19111, United States (Kaufmann) Departments of Oncology and Molecular Pharmacology, Mayo Clinic, Rochester, MN 55905, United States (Lin, Harding) Clovis Oncology, Boulder, CO 80301, United States (deFazio) Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney Medical School, The University of Sydney and Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW 2145, Australia (McNeish) Division of Cancer, Department of Surgery and Cancer, Imperial College London, Kensington, London SW7 2AZ, United Kingdom (Wakefield) Melbourne Bioinformatics, University of Melbourne, Melbourne, VIC 3010, Australia (Chenevix-Trench, Green, Webb, Moore, Harrap, Sadkowsky, Pandeya, Malt, Alexander, Ashover, Brown, Corrish, Green, Jackman, Ferguson, Martin, Martyn, Ranieri, Purdie, Whiteman) QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia (Gertig) Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia (Fereday, Bowes, Galletta, Giles, Hendley, Phillips, Rischin, Fox, Johnson, Lade, Loughrey, O'Callaghan, Murray) Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia (Hung, Chiew, Stenlake, Sullivan) Centre for Cancer Research, The Westmead Millennium Institute for Medical Research, The University of Sydney and Departments of Gynaecological Oncology, Westmead Hospital, Sydney, NSW 2145, Australia (Mellon, Robertson, Proietto, Braye, Otton) John Hunter Hospital, Lookout Road, New Lambton, NSW 2305, Australia (Vanden Bergh, Jones, Mackenzie, Camaris, Crouch, Edwards, Hacker, Marsden, Robertson) Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia (Maidens, Bell, Baron-Hay, Ferrier, Gard, Nevell, Pavlakis, Valmadre, Young) Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065, Australia (Nattress, Beale, Beith, Carter, Dalrymple, Houghton, Russell) Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia (White, Davy, Oehler, Hall, Dodd) Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia (Jayde, Blomfield, Challis, McIntosh, Parker) Royal Hobart Hospital, 48 Liverpool St, Hobart, TAS 7000, Australia (Mamers, Healy, Jobling, Manolitsas, McNealage, Rogers, Susil, Sumithran, Simpson) Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia (Schmidt, Shirley, Viduka, Tran, Bilic, Glavinas, Pittman, Zeps) Western Australian Research Tissue Network (WARTN), St John of God Pathology, 23 Walters Drive, Osborne Park, WA 6017, Australia (Ball, Young, Hammond, Leung, McCartney) Women and Infant's Research Foundation, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia (Brooks, Pierdes) St John of God Hospital, 12 Salvado Rd, Subiaco, WA 6008, Australia (Stuart-Harris) Canberra Hospital, Yamba Drive, Garran, ACT 2605, Australia (Kirsten) Bankstown Cancer Centre, Bankstown Hospital, 70 Eldridge Road, Bankstown, NSW 2200, Australia (Rutovitz) Northern Haematology & Oncology Group, Integrated Cancer Centre, 185 Fox Valley Road, Wahroonga, NSW 2076, Australia (Clingan, Glasgow) Illawarra Shoalhaven Local Health District, Wollongong Hospital, Level 4 Lawson House, Wollongong, NSW 2500, Australia (Shannon) Nepean Hospital, Derby Street, Kingswood, NSW 2747, Australia (Bonaventura, Stewart) Newcastle Mater Misericordiae Hospital, Edith Street, Waratah, NSW 2298, Australia (Begbie) Port Macquarie Base Hospital, Wrights Road, Port Macquarie, NSW 2444, Australia (Friedlander) Prince of Wales Clinical School, University of Sydney, Sydney, NSW 2031, Australia (Links) St George Hospital, Gray Street, Kogarah, NSW 2217, Australia (Grygiel) St Vincent's Hospital, 390 Victoria Street, Darlinghurst, NSW 2010, Australia (Hill) Wagga Wagga Base Hospital, Docker St, Wagga Wagga, NSW 2650, Australia (Brand, Byth, Jaworski, Harnett, Wain) Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia (Sharma) Department of Pathology, Westmead Clinical School, Westmead Hospital, The University of Sydney, Sydney, NSW 2006, Australia (Ward, Papadimos) Mater Misericordiae Hospital, Raymond Terrace, South Brisbane, QLD 4101, Australia (Crandon, Cummings, Horwood, Obermair, Perrin, Wyld, Nicklin) The Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD 4006, Australia (Nicklin) Wesley Hospital, 451 Coronation Drive, Auchenflower, QLD 4066, Australia (Healy) Burnside Hospital, 120 Kensington Road, Toorak Gardens, SA 5065, Australia (Henderson) Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042, Australia (Miller) Queen Elizabeth Hospital, 28 Woodville Road, Woodville South, SA 5011, Australia (Brown, Rome) Freemasons Hospital, 20 Victoria Parade, East Melbourne, VIC 3002, Australia (Allen, Grant, Hyde, Laurie, Robbie) Mercy Hospital for Women, 163 Studley Road, Heidelberg, VIC 3084, Australia (Waring) Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia (Underhill) Border Medical Oncology, Nordsvan Dr and Pearce Dr, Wodonga, VIC 3690, Australia (Bell) Andrew Love Cancer Centre, 70 Swanston Street, Geelong, VIC 3220, Australia (Ng) Ballarat Base Hospital, Drummond Street North, Ballarat, VIC 3350, Australia (Blum) Bendigo Health Care Group, 62 Lucan Street, Bendigo, VIC 3550, Australia (Ganju) Peninsula Health, 2 Hastings Road, Frankston, VIC 3199, Australia (Buck) Mount Hospital, 150 Mounts Bay Road, Perth, WA 6000, Australia (Haviv) Faculty of Medicine, Bar-Ilan University, 8 Henrietta Szold St, Safed 1311502, Israel | Issue Date: | 8-Oct-2018 | Copyright year: | 2018 | Publisher: | Nature Publishing Group (Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Nature Communications. 9 (1) (no pagination), 2018. Article Number: 3970. Date of Publication: 01 Dec 2018. | Journal: | Nature Communications | Abstract: | Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s). | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1038/s41467-018-05564-z | ORCID: | Kondrashova, Olga; ORCID: http://orcid.org/0000-0003-0022-5149 Wakefield, Matthew J.; ORCID: http://orcid.org/0000-0001-6624-4698 Scott, Clare L.; ORCID: http://orcid.org/0000-0002-3689-5956 Pearson, Richard B.; ORCID: http://orcid.org/0000-0001-5919-5090 Kaufmann, Scott H.; ORCID: http://orcid.org/0000-0002-4900-7145 McNeish, Iain A.; ORCID: http://orcid.org/0000-0002-9387-7586 | PubMed URL: | 30266954 [http://www.ncbi.nlm.nih.gov/pubmed/?term=30266954] | ISSN: | 2041-1723 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37301 | Type: | Article |
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