Now showing items 1-20 of 71

    • A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers. 

      Coignard, J; Lush, M; Beesley, J; O'Mara, TA; Dennis, J; Tyrer, JP; Barnes, DR; McGuffog, L; Leslie, G; Bolla, MK; Adank, MA; Agata, S; Ahearn, T; Aittomäki, K; Andrulis, IL; Anton-Culver, H; Arndt, V; Arnold, N; Aronson, KJ; Arun, BK; Augustinsson, A; Azzollini, J; Barrowdale, D; Baynes, C; Becher, H; Bermisheva, M; Bernstein, L; Białkowska, K; Blomqvist, C; Bojesen, SE; Bonanni, B; Borg, A; Brauch, H; Brenner, H; Burwinkel, B; Buys, SS; Caldés, T; Caligo, MA; Campa, D; Carter, BD; Castelao, JE; Chang-Claude, J; Chanock, SJ; Chung, WK; Claes, KBM; Clarke, CL; GEMO Study Collaborators; EMBRACE Collaborators; Collée, JM; Conroy, DM; Czene, K; Daly, MB; Devilee, P; Diez, O; Ding, YC; Domchek, SM; Dörk, T; Dos-Santos-Silva, I; Dunning, AM; Dwek, M; Eccles, DM; Eliassen, AH; Engel, C; Eriksson, M; Evans, DG; Fasching, PA; Flyger, H; Fostira, F; Friedman, E; Fritschi, L; Frost, D; Gago-Dominguez, M; Gapstur, SM; Garber, J; Garcia-Barberan, V; García-Closas, M; García-Sáenz, JA; Gaudet, MM; Gayther, SA; Gehrig, A; Georgoulias, V; Giles, GG; Godwin, AK; Goldberg, MS; Goldgar, DE; González-Neira, A; Greene, MH; Guénel, P; Haeberle, L; Hahnen, E; Haiman, CA; Håkansson, N; Hall, P; Hamann, U; Harrington, PA; Hart, SN; He, W; Hogervorst, FBL; Hollestelle, A; Hopper, JL; Horcasitas, DJ; Hulick, PJ; Hunter, DJ; Imyanitov, EN; KConFab Investigators; HEBON Investigators; ABCTB Investigators; Jager, A; Jakubowska, A; James, PA; Jensen, UB; John, EM; Jones, ME; Kaaks, R; Kapoor, PM; Karlan, BY; Keeman, R; Khusnutdinova, E; Kiiski, JI; Ko, Y-D; Kosma, V-M; Kraft, P; Kurian, AW; Laitman, Y; Lambrechts, D; Le Marchand, L; Lester, J; Lesueur, F; Lindstrom, T; Lopez-Fernández, A; Loud, JT; Luccarini, C; Mannermaa, A; Manoukian, S; Margolin, S; Martens, JWM; Mebirouk, N; Meindl, A; Miller, A; Milne, RL; Montagna, M; Nathanson, KL; Neuhausen, SL; Nevanlinna, H; Nielsen, FC; O'Brien, KM; Olopade, OI; Olson, JE; Olsson, H; Osorio, A; Ottini, L; Park-Simon, T-W; Parsons, MT; Pedersen, IS; Peshkin, B; Peterlongo, P; Peto, J; Pharoah, PDP; Phillips, K-A; Polley, EC; Poppe, B; Presneau, N; Pujana, MA; Punie, K; Radice, P; Rantala, J; Rashid, MU; Rennert, G; Rennert, HS; Robson, M; Romero, A; Rossing, M; Saloustros, E; Sandler, DP; Santella, R; Scheuner, MT; Schmidt, MK; Schmidt, G; Scott, C; Sharma, P; Soucy, P; Southey, MC; Spinelli, JJ; Steinsnyder, Z; Stone, J; Stoppa-Lyonnet, D; Swerdlow, A; Tamimi, RM; Tapper, WJ; Taylor, JA; Terry, MB; Teulé, A; Thull, DL; Tischkowitz, M; Toland, AE; Torres, D; Trainer, AH; Truong, T; Tung, N; Vachon, CM; Vega, A; Vijai, J; Wang, Q; Wappenschmidt, B; Weinberg, CR; Weitzel, JN; Wendt, C; Wolk, A; Yadav, S; Yang, XR; Yannoukakos, D; Zheng, W; Ziogas, A; Zorn, KK; Park, SK; Thomassen, M; Offit, K; Schmutzler, RK; Couch, FJ; Simard, J; Chenevix-Trench, G; Easton, DF; Andrieu, N; Antoniou, AC (2021-02-17)
      Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in ...
    • A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events. 

      Ryan, CJ; Kennedy, S; Bajrami, I; Matallanas, D; Lord, CJ (2017-10-11)
      Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and abundance varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a ...
    • Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease. 

      Simigdala, N; Pancholi, S; Ribas, R; Folkerd, E; Liccardi, G; Nikitorowicz-Buniak, J; Johnston, SR; Dowsett, M; Martin, L-A (2018-08)
      Background Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of metastatic ...
    • Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration. 

      Croft, DR; Coleman, ML; Li, S; Robertson, D; Sullivan, T; Stewart, CL; Olson, MF (2005-01)
      Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and ...
    • BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. 

      Turner, NC; Alarcón, E; Armstrong, AC; Philco, M; López Chuken, YA; Sablin, M-P; Tamura, K; Gómez Villanueva, A; Pérez-Fidalgo, JA; Cheung, SYA; Corcoran, C; Cullberg, M; Davies, BR; de Bruin, EC; Foxley, A; Lindemann, JPO; Maudsley, R; Moschetta, M; Outhwaite, E; Pass, M; Rugman, P; Schiavon, G; Oliveira, M (2019-05)
      Background BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1-3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive ...
    • Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. 

      Yost, S; de Wolf, B; Hanks, S; Zachariou, A; Marcozzi, C; Clarke, M; de Voer, R; Etemad, B; Uijttewaal, E; Ramsay, E; Wylie, H; Elliott, A; Picton, S; Smith, A; Smithson, S; Seal, S; Ruark, E; Houge, G; Pines, J; Kops, GJPL; Rahman, N (2017-07)
      Through exome sequencing, we identified six individuals with biallelic loss-of-function mutations in TRIP13. All six developed Wilms tumor. Constitutional mosaic aneuploidies, microcephaly, developmental delay and seizures, ...
    • Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer. 

      Bianchini, G; Kiermaier, A; Bianchi, GV; Im, Y-H; Pienkowski, T; Liu, M-C; Tseng, L-M; Dowsett, M; Zabaglo, L; Kirk, S; Szado, T; Eng-Wong, J; Amler, LC; Valagussa, P; Gianni, L (2017-02-09)
      Background NeoSphere showed significantly higher pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and docetaxel compared with trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab ...
    • Capture Hi-C identifies putative target genes at 33 breast cancer risk loci. 

      Baxter, JS; Leavy, OC; Dryden, NH; Maguire, S; Johnson, N; Fedele, V; Simigdala, N; Martin, L-A; Andrews, S; Wingett, SW; Assiotis, I; Fenwick, K; Chauhan, R; Rust, AG; Orr, N; Dudbridge, F; Haider, S; Fletcher, O (2018-03-12)
      Genome-wide association studies (GWAS) have identified approximately 100 breast cancer risk loci. Translating these findings into a greater understanding of the mechanisms that influence disease risk requires identification ...
    • Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. 

      Tutt, A; Tovey, H; Cheang, MCU; Kernaghan, S; Kilburn, L; Gazinska, P; Owen, J; Abraham, J; Barrett, S; Barrett-Lee, P; Brown, R; Chan, S; Dowsett, M; Flanagan, JM; Fox, L; Grigoriadis, A; Gutin, A; Harper-Wynne, C; Hatton, MQ; Hoadley, KA; Parikh, J; Parker, P; Perou, CM; Roylance, R; Shah, V; Shaw, A; Smith, IE; Timms, KM; Wardley, AM; Wilson, G; Gillett, C; Lanchbury, JS; Ashworth, A; Rahman, N; Harries, M; Ellis, P; Pinder, SE; Bliss, JM (2018-05)
      Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs ...
    • CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
      Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
    • Cells Lacking the <i>RB1</i> Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. 

      Oser, MG; Fonseca, R; Chakraborty, AA; Brough, R; Spektor, A; Jennings, RB; Flaifel, A; Novak, JS; Gulati, A; Buss, E; Younger, ST; McBrayer, SK; Cowley, GS; Bonal, DM; Nguyen, Q-D; Brulle-Soumare, L; Taylor, P; Cairo, S; Ryan, CJ; Pease, EJ; Maratea, K; Travers, J; Root, DE; Signoretti, S; Pellman, D; Ashton, S; Lord, CJ; Barry, ST; Kaelin, WG (2019-02)
      Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating <i>RB1</i> and <i>TP53</i> mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical ...
    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CKY; Wai, P; Lambros, MB; Samartzis, EP; Dedes, KJ; Frankum, J; Bajrami, I; Kopec, A; Mackay, A; A'hern, R; Fenwick, K; Kozarewa, I; Hakas, J; Mitsopoulos, C; Hardisson, D; Lord, CJ; Kumar-Sinha, C; Ashworth, A; Weigelt, B; Sapino, A; Chinnaiyan, AM; Maher, CA; Reis-Filho, JS (2014-04)
      Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen ...
    • 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) ...
    • Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. 

      Goodall, J; Mateo, J; Yuan, W; Mossop, H; Porta, N; Miranda, S; Perez-Lopez, R; Dolling, D; Robinson, DR; Sandhu, S; Fowler, G; Ebbs, B; Flohr, P; Seed, G; Rodrigues, DN; Boysen, G; Bertan, C; Atkin, M; Clarke, M; Crespo, M; Figueiredo, I; Riisnaes, R; Sumanasuriya, S; Rescigno, P; Zafeiriou, Z; Sharp, A; Tunariu, N; Bianchini, D; Gillman, A; Lord, CJ; Hall, E; Chinnaiyan, AM; Carreira, S; de Bono, JS; TOPARP-A investigators (2017-09)
      Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ...
    • Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial. 

      Turner, NC; Kingston, B; Kilburn, LS; Kernaghan, S; Wardley, AM; Macpherson, IR; Baird, RD; Roylance, R; Stephens, P; Oikonomidou, O; Braybrooke, JP; Tuthill, M; Abraham, J; Winter, MC; Bye, H; Hubank, M; Gevensleben, H; Cutts, R; Snowdon, C; Rea, D; Cameron, D; Shaaban, A; Randle, K; Martin, S; Wilkinson, K; Moretti, L; Bliss, JM; Ring, A (2020-10)
      Background Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in ...
    • Comparison of BEAMing and Droplet Digital PCR for Circulating Tumor DNA Analysis. 

      O'Leary, B; Hrebien, S; Beaney, M; Fribbens, C; Garcia-Murillas, I; Jiang, J; Li, Y; Huang Bartlett, C; André, F; Loibl, S; Loi, S; Cristofanilli, M; Turner, NC (2019-11)
      Background Circulating tumor DNA (ctDNA) assays are increasingly used for clinical decision-making, but it is unknown how well different assays agree. We aimed to assess the agreement in ctDNA mutation calling between ...
    • CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting. 

      Münz, M; Ruark, E; Renwick, A; Ramsay, E; Clarke, M; Mahamdallie, S; Cloke, V; Seal, S; Strydom, A; Lunter, G; Rahman, N (2015-07-28)
      Next-generation sequencing (NGS) offers unprecedented opportunities to expand clinical genomics. It also presents challenges with respect to integration with data from other sequencing methods and historical data. Provision ...
    • De Novo Truncating Mutations in the Last and Penultimate Exons of PPM1D Cause an Intellectual Disability Syndrome. 

      Jansen, S; Geuer, S; Pfundt, R; Brough, R; Ghongane, P; Herkert, JC; Marco, EJ; Willemsen, MH; Kleefstra, T; Hannibal, M; Shieh, JT; Lynch, SA; Flinter, F; FitzPatrick, DR; Gardham, A; Bernhard, B; Ragge, N; Newbury-Ecob, R; Bernier, R; Kvarnung, M; Magnusson, EAH; Wessels, MW; van Slegtenhorst, MA; Monaghan, KG; de Vries, P; Veltman, JA; Deciphering Developmental Disorders Study; Lord, CJ; Vissers, LELM; de Vries, BBA (2017-04)
      Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically ...
    • Directing the use of DDR kinase inhibitors in cancer treatment. 

      Brandsma, I; Fleuren, EDG; Williamson, CT; Lord, CJ (2017-12)
      Introduction Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval ...
    • Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance. 

      Martin, L-A; Ribas, R; Simigdala, N; Schuster, E; Pancholi, S; Tenev, T; Gellert, P; Buluwela, L; Harrod, A; Thornhill, A; Nikitorowicz-Buniak, J; Bhamra, A; Turgeon, M-O; Poulogiannis, G; Gao, Q; Martins, V; Hills, M; Garcia-Murillas, I; Fribbens, C; Patani, N; Li, Z; Sikora, MJ; Turner, N; Zwart, W; Oesterreich, S; Carroll, J; Ali, S; Dowsett, M (2017-11-30)
      Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, ...