Now showing items 1-10 of 10

    • Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. 

      Holme, H; Gulati, A; Brough, R; Fleuren, EDG; Bajrami, I; Campbell, J; Chong, IY; Costa-Cabral, S; Elliott, R; Fenton, T; Frankum, J; Jones, SE; Menon, M; Miller, R; Pemberton, HN; Postel-Vinay, S; Rafiq, R; Selfe, JL; von Kriegsheim, A; Munoz, AG; Rodriguez, J; Shipley, J; van der Graaf, WTA; Williamson, CT; Ryan, CJ; Pettitt, S; Ashworth, A; Strauss, SJ; Lord, CJ (2018-07-13)
      Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...
    • Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. 

      Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; Stoynov, SS; Ashworth, A; Lord, CJ (2018-05-22)
      Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...
    • E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. 

      Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; Frankum, J; Song, F; Rafiq, R; Konde, A; Krastev, DB; Menon, M; Campbell, J; Gulati, A; Kumar, R; Pettitt, SJ; Gurden, MD; Cardenosa, ML; Chong, I; Gazinska, P; Wallberg, F; Sawyer, EJ; Martin, L-A; Dowsett, M; Linardopoulos, S; Natrajan, R; Ryan, CJ; Derksen, PWB; Jonkers, J; Tutt, ANJ; Ashworth, A; Lord, CJ (2018-04)
      The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
    • Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. 

      Nikkilä, J; Kumar, R; Campbell, J; Brandsma, I; Pemberton, HN; Wallberg, F; Nagy, K; Scheer, I; Vertessy, BG; Serebrenik, AA; Monni, V; Harris, RS; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-06-27)
      BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells. 

      Pettitt, SJ; Krastev, DB; Pemberton, HN; Fontebasso, Y; Frankum, J; Rehman, FL; Brough, R; Song, F; Bajrami, I; Rafiq, R; Wallberg, F; Kozarewa, I; Fenwick, K; Armisen-Garrido, J; Swain, A; Gulati, A; Campbell, J; Ashworth, A; Lord, CJ (2017-03-01)
      We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ...
    • Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer. 

      Brough, R; Gulati, A; Haider, S; Kumar, R; Campbell, J; Knudsen, E; Pettitt, SJ; Ryan, CJ; Lord, CJ (2018-10)
      Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating ...
    • Modeling Therapy Resistance in BRCA1/2-Mutant Cancers. 

      Dréan, A; Williamson, CT; Brough, R; Brandsma, I; Menon, M; Konde, A; Garcia-Murillas, I; Pemberton, HN; Frankum, J; Rafiq, R; Badham, N; Campbell, J; Gulati, A; Turner, NC; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-09)
      Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ...
    • The shieldin complex mediates 53BP1-dependent DNA repair. 

      Noordermeer, SM; Adam, S; Setiaputra, D; Barazas, M; Pettitt, SJ; Ling, AK; Olivieri, M; Álvarez-Quilón, A; Moatti, N; Zimmermann, M; Annunziato, S; Krastev, DB; Song, F; Brandsma, I; Frankum, J; Brough, R; Sherker, A; Landry, S; Szilard, RK; Munro, MM; McEwan, A; Goullet de Rugy, T; Lin, Z-Y; Hart, T; Moffat, J; Gingras, A-C; Martin, A; van Attikum, H; Jonkers, J; Lord, CJ; Rottenberg, S; Durocher, D (2018-08)
      53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14-9, ...