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dc.contributor.authorKondrashova, O
dc.contributor.authorTopp, M
dc.contributor.authorNesic, K
dc.contributor.authorLieschke, E
dc.contributor.authorHo, G-Y
dc.contributor.authorHarrell, M
dc.contributor.authorZapparoli, G
dc.contributor.authorHadley, A
dc.contributor.authorHolian, R
dc.contributor.authorBoehm, E
dc.contributor.authorHeong, V
dc.contributor.authorSanij, E
dc.contributor.authorPearson, RB
dc.contributor.authorKrais, JJ
dc.contributor.authorJohnson, N
dc.contributor.authorMcNally, O
dc.contributor.authorAnanda, S
dc.contributor.authorAlsop, K
dc.contributor.authorHutt, KJ
dc.contributor.authorKaufmann, SH
dc.contributor.authorLin, KK
dc.contributor.authorHarding, TC
dc.contributor.authorTraficante, N
dc.contributor.authordeFazio, A
dc.contributor.authorMcNeish, LA
dc.contributor.authorBowtell, DD
dc.contributor.authorSwisher, EM
dc.contributor.authorDobrovic, A
dc.contributor.authorWakefield, MJ
dc.contributor.authorScott, CL
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorGreen, A
dc.contributor.authorWebb, P
dc.contributor.authorGertig, D
dc.contributor.authorFereday, S
dc.contributor.authorMoore, S
dc.contributor.authorHung, J
dc.contributor.authorHarrap, K
dc.contributor.authorSadkowsky, T
dc.contributor.authorPandeya, N
dc.contributor.authorMalt, M
dc.contributor.authorMellon, A
dc.contributor.authorRobertson, R
dc.contributor.authorVanden Bergh, T
dc.contributor.authorJones, M
dc.contributor.authorMackenzie, P
dc.contributor.authorMaidens, J
dc.contributor.authorNattress, K
dc.contributor.authorChiew, YE
dc.contributor.authorStenlake, A
dc.contributor.authorSullivan, H
dc.contributor.authorAlexander, B
dc.contributor.authorAshover, P
dc.contributor.authorBrown, S
dc.contributor.authorCorrish, T
dc.contributor.authorGreen, L
dc.contributor.authorJackman, L
dc.contributor.authorFerguson, K
dc.contributor.authorMartin, K
dc.contributor.authorMartyn, A
dc.contributor.authorRanieri, B
dc.contributor.authorWhite, J
dc.contributor.authorJayde, V
dc.contributor.authorMamers, P
dc.contributor.authorBowes, L
dc.contributor.authorGalletta, L
dc.contributor.authorGiles, D
dc.contributor.authorHendley, J
dc.contributor.authorSchmidt, T
dc.contributor.authorShirley, H
dc.contributor.authorBall, C
dc.contributor.authorYoung, C
dc.contributor.authorViduka, S
dc.contributor.authorTran, H
dc.contributor.authorBilic, S
dc.contributor.authorGlavinas, L
dc.contributor.authorBrooks, J
dc.contributor.authorStuart-Harris, R
dc.contributor.authorKirsten, F
dc.contributor.authorRutovitz, J
dc.contributor.authorClingan, P
dc.contributor.authorGlasgow, A
dc.contributor.authorProietto, A
dc.contributor.authorBraye, S
dc.contributor.authorOtton, G
dc.contributor.authorShannon, J
dc.contributor.authorBonaventura, T
dc.contributor.authorStewart, J
dc.contributor.authorBegbie, S
dc.contributor.authorFriedlander, M
dc.contributor.authorBell, D
dc.contributor.authorBaron-Hay, S
dc.contributor.authorFerrier, A
dc.contributor.authorGard, G
dc.contributor.authorNevell, D
dc.contributor.authorPavlakis, N
dc.contributor.authorValmadre, S
dc.contributor.authorYoung, B
dc.contributor.authorCamaris, C
dc.contributor.authorCrouch, R
dc.contributor.authorEdwards, L
dc.contributor.authorHacker, N
dc.contributor.authorMarsden, D
dc.contributor.authorRobertson, G
dc.contributor.authorBeale, P
dc.contributor.authorBeith, J
dc.contributor.authorCarter, J
dc.contributor.authorDalrymple, C
dc.contributor.authorHoughton, R
dc.contributor.authorRussell, P
dc.contributor.authorLinks, M
dc.contributor.authorGrygiel, J
dc.contributor.authorHill, J
dc.contributor.authorBrand, A
dc.contributor.authorByth, K
dc.contributor.authorJaworski, R
dc.contributor.authorHarnett, P
dc.contributor.authorSharma, R
dc.contributor.authorWain, G
dc.contributor.authorWard, B
dc.contributor.authorPapadimos, D
dc.contributor.authorCrandon, A
dc.contributor.authorCummings, M
dc.contributor.authorHorwood, K
dc.contributor.authorObermair, A
dc.contributor.authorPerrin, L
dc.contributor.authorWyld, D
dc.contributor.authorNicklin, J
dc.contributor.authorDavy, M
dc.contributor.authorOehler, MK
dc.contributor.authorHall, C
dc.contributor.authorDodd, T
dc.contributor.authorHealy, T
dc.contributor.authorPittman, K
dc.contributor.authorHenderson, D
dc.contributor.authorMiller, J
dc.contributor.authorPierdes, J
dc.contributor.authorBlomfield, P
dc.contributor.authorChallis, D
dc.contributor.authorMclntosh, R
dc.contributor.authorParker, A
dc.contributor.authorBrown, B
dc.contributor.authorRome, R
dc.contributor.authorAllen, D
dc.contributor.authorGrant, P
dc.contributor.authorHyde, S
dc.contributor.authorLaurie, R
dc.contributor.authorRobbie, M
dc.contributor.authorHealy, D
dc.contributor.authorJobling, T
dc.contributor.authorManolitsas, T
dc.contributor.authorMcNealage, J
dc.contributor.authorRogers, P
dc.contributor.authorSusil, B
dc.contributor.authorSumithran, E
dc.contributor.authorSimpson, I
dc.contributor.authorPhillips, K
dc.contributor.authorRischin, D
dc.contributor.authorFox, S
dc.contributor.authorJohnson, D
dc.contributor.authorLade, S
dc.contributor.authorLoughrey, M
dc.contributor.authorO'Callaghan, N
dc.contributor.authorMurray, W
dc.contributor.authorWaring, P
dc.contributor.authorBillson, V
dc.contributor.authorPyman, J
dc.contributor.authorNeesham, D
dc.contributor.authorQuinn, M
dc.contributor.authorUnderhill, C
dc.contributor.authorBell, R
dc.contributor.authorNg, LF
dc.contributor.authorBlum, R
dc.contributor.authorGanju, V
dc.contributor.authorHammond, I
dc.contributor.authorLeung, Y
dc.contributor.authorMcCartney, A
dc.contributor.authorBuck, M
dc.contributor.authorHaviv, I
dc.contributor.authorPurdie, D
dc.contributor.authorWhiteman, D
dc.contributor.authorZeps, N
dc.date.available2019-03-18T21:49:55Z
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.available2018-06-25
dc.date.issued2018-09-28
dc.identifierpii: 10.1038/s41467-018-05564-z
dc.identifier.citationKondrashova, O., Topp, M., Nesic, K., Lieschke, E., Ho, G. -Y., Harrell, M., Zapparoli, G., 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. ,... Zeps, N. (2018). Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-05564-z.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/221537
dc.description.abstractAccurately 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleMethylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-018-05564-z
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentMedicine, Dentistry & Health Sciences
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentMedicine (St Vincent's)
melbourne.affiliation.departmentMedicine, Western Health
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleNATURE COMMUNICATIONS
melbourne.source.volume9
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1350320
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162272
melbourne.contributor.authorWakefield, Matthew
melbourne.contributor.authorKondrashova, Olga
melbourne.contributor.authorNesic, Ksenija
melbourne.contributor.authorLieschke, Elizabeth
melbourne.contributor.authorHo, Gwo Yaw
melbourne.contributor.authorHOLIAN, ROBERT
melbourne.contributor.authorBOEHM, EMMA
melbourne.contributor.authorHeong, Valerie
melbourne.contributor.authorSanij, Elaine
melbourne.contributor.authorPearson, Richard
melbourne.contributor.authorMcNally, Orla
melbourne.contributor.authorAnanda, Sumitra
melbourne.contributor.authorBowtell, David
melbourne.contributor.authorScott, Clare
melbourne.contributor.authorDobrovic, Alexander
melbourne.contributor.authorHaviv, Izhak
melbourne.contributor.authorNeesham, Deborah
melbourne.contributor.authorPyman, Jan
melbourne.contributor.authorRome, Robert
melbourne.contributor.authorWaring, Paul
dc.identifier.eissn2041-1723
melbourne.identifier.fundernameidNational Health and Medical Research Council, 1062702
melbourne.identifier.fundernameidWALTER & ELIZA HALL INSTITUTE OF MEDICAL RESEARCH
pubs.acceptance.date2018-06-25
melbourne.accessrightsOpen Access


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