Medicine, Dentistry & Health Sciences Collected Works - Research Publications

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http://hdl.handle.net/11343/241

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Author: Bowtell, David ×

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    Molecular comparison of pure ovarian fibroma with serous benign ovarian tumours
    Hunter, SM ; Dall, GV ; Doyle, MA ; Lupat, R ; Li, J ; Allan, P ; Rowley, SM ; Bowtell, D ; Campbell, IG ; Gorringe, KL (SPRINGERNATURE, 2020-07-22)
    OBJECTIVE: Ovarian fibromas and adenofibromas are rare ovarian tumours. They are benign tumours composed of spindle-like stromal cells (pure fibroma) or a mixture of fibroblast and epithelial components (adenofibroma). We have previously shown that 40% of benign serous ovarian tumours are likely primary fibromas due to the neoplastic alterations being restricted to the stromal compartment of these tumours. We further explore this finding by comparing benign serous tumours to pure fibromas. RESULTS: Performing copy number aberration (CNA) analysis on the stromal component of 45 benign serous tumours and 8 pure fibromas, we have again shown that trisomy of chromosome 12 is the most common aberration in ovarian fibromas. CNAs were more frequent in the pure fibromas than the benign serous tumours (88% vs 33%), however pure fibromas more frequently harboured more than one CNA event compared with benign serous tumours. As these extra CNA events observed in the pure fibromas were unique to this subset our data indicates a unique tumour evolution. Gene expression analysis on the two cohorts was unable to show gene expression changes that differed based on tumour subtype. Exome analysis did not reveal any recurrently mutated genes.
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    Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma
    Kondrashova, 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, RB ; Krais, JJ ; Johnson, N ; McNally, O ; Ananda, S ; Alsop, K ; Hutt, KJ ; Kaufmann, SH ; Lin, KK ; Harding, TC ; Traficante, N ; deFazio, A ; McNeish, LA ; Bowtell, DD ; Swisher, EM ; Dobrovic, A ; Wakefield, MJ ; Scott, CL ; 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 ; Vanden Bergh, T ; Jones, M ; Mackenzie, P ; Maidens, J ; Nattress, K ; Chiew, YE ; Stenlake, A ; Sullivan, H ; Alexander, B ; Ashover, P ; Brown, S ; Corrish, T ; Green, L ; Jackman, L ; Ferguson, K ; Martin, K ; Martyn, A ; Ranieri, B ; White, J ; Jayde, V ; Mamers, P ; Bowes, L ; Galletta, 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 ; 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 ; 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, MK ; Hall, C ; Dodd, T ; Healy, T ; Pittman, K ; Henderson, D ; Miller, J ; Pierdes, J ; Blomfield, P ; Challis, D ; Mclntosh, R ; Parker, A ; Brown, B ; Rome, R ; Allen, D ; Grant, P ; Hyde, S ; Laurie, R ; Robbie, M ; Healy, D ; Jobling, T ; 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 ; Bell, R ; Ng, LF ; Blum, R ; Ganju, V ; Hammond, I ; Leung, Y ; McCartney, A ; Buck, M ; Haviv, I ; Purdie, D ; Whiteman, D ; Zeps, N (NATURE PUBLISHING GROUP, 2018-09-28)
    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.
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    Precision Medicine: Dawn of Supercomputing in ‘omics Research
    Reumann, M ; Holt, KE ; Inouye, M ; Stinear, T ; Goudey, B ; Abraham, G ; WANG, Q ; Shi, F ; Kowalczyk, A ; Pearce, A ; Isaac, A ; Pope, BJ ; Butzkueven, H ; Wagner, J ; Moore, S ; Downton, M ; Church, PC ; Turner, SJ ; Field, J ; Southey, M ; Bowtell, D ; Schmidt, D ; Makalic, E ; Zobel, J ; Hopper, J ; Petrovski, S ; O'Brien, T (eResearch Australasia, 2011)