Now showing items 1-20 of 34

    • 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer. 

      Peck, B; Bland, P; Mavrommati, I; Muirhead, G; Cottom, H; Wai, PT; Maguire, SL; Barker, HE; Morrison, E; Kriplani, D; Yu, L; Gibson, A; Falgari, G; Brennan, K; Farnie, G; Buus, R; Marlow, R; Novo, D; Knight, E; Guppy, N; Kolarevic, D; Susnjar, S; Milijic, NM; Naidoo, K; Gazinska, P; Roxanis, I; Pancholi, S; Martin, L-A; Holgersen, EM; Cheang, MCU; Noor, F; Postel-Vinay, S; Quinn, G; McDade, S; Krasny, L; Huang, P; Daley, F; Wallberg, F; Choudhary, JS; Haider, S; Tutt, AN; Natrajan, R (2021-01-28)
      Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies ...
    • An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. 

      Maley, CC; Koelble, K; Natrajan, R; Aktipis, A; Yuan, Y (2015-09-22)
      Introduction Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have ...
    • 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 ...
    • Comparative proteomic assessment of matrisome enrichment methodologies. 

      Krasny, L; Paul, A; Wai, P; Howard, BA; Natrajan, RC; Huang, PH (2016-11)
      The matrisome is a complex and heterogeneous collection of extracellular matrix (ECM) and ECM-associated proteins that play important roles in tissue development and homeostasis. While several strategies for matrisome ...
    • Driver Oncogenes but Not as We Know Them: Targetable Fusion Genes in Breast Cancer. 

      Natrajan, R; Tutt, ANJ; Lord, CJ (2018-03)
      <b/> Two reports in this issue of Cancer Discovery outline how the genomic composition of tumors, including the presence of intragenic gene fusions, could inform the selection of treatment approaches in aggressive forms ...
    • Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors. 

      Wong, JP; Todd, JR; Finetti, MA; McCarthy, F; Broncel, M; Vyse, S; Luczynski, MT; Crosier, S; Ryall, KA; Holmes, K; Payne, LS; Daley, F; Wai, P; Jenks, A; Tanos, B; Tan, A-C; Natrajan, RC; Williamson, D; Huang, PH (2016-10)
      Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF ...
    • 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 ...
    • Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer. 

      Naidoo, K; Wai, PT; Maguire, SL; Daley, F; Haider, S; Kriplani, D; Campbell, J; Mirza, H; Grigoriadis, A; Tutt, A; Moseley, PM; Abdel-Fatah, TMA; Chan, SYT; Madhusudan, S; Rhaka, EA; Ellis, IO; Lord, CJ; Yuan, Y; Green, AR; Natrajan, R (2018-01)
      Disruption of Cyclin-Dependent Kinase 12 (<i>CDK12</i>) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, <i>CDK12</i> has also been proposed as an oncogene in ...
    • From integrative genomics to therapeutic targets. 

      Natrajan, R; Wilkerson, P (2013-06-05)
      Combinatorial approaches that integrate conventional pathology with genomic profiling and functional genomics have begun to enhance our understanding of the genetic basis of breast cancer. These methods have identified key ...
    • Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast. 

      Piscuoglio, S; Ng, CKY; Geyer, FC; Burke, KA; Cowell, CF; Martelotto, LG; Natrajan, R; Popova, T; Maher, CA; Lim, RS; Bruijn, ID; Mariani, O; Norton, L; Vincent-Salomon, A; Weigelt, B; Reis-Filho, JS
      Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal ...
    • Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation. 

      Dalton, WB; Helmenstine, E; Walsh, N; Gondek, LP; Kelkar, DS; Read, A; Natrajan, R; Christenson, ES; Roman, B; Das, S; Zhao, L; Leone, RD; Shinn, D; Groginski, T; Madugundu, AK; Patil, A; Zabransky, DJ; Medford, A; Lee, J; Cole, AJ; Rosen, M; Thakar, M; Ambinder, A; Donaldson, J; DeZern, AE; Cravero, K; Chu, D; Madero-Marroquin, R; Pandey, A; Hurley, PJ; Lauring, J; Park, BH (2019-08-08)
      Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are ...
    • Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes. 

      Clarke, M; Mackay, A; Ismer, B; Pickles, JC; Tatevossian, RG; Newman, S; Bale, TA; Stoler, I; Izquierdo, E; Temelso, S; Carvalho, DM; Molinari, V; Burford, A; Howell, L; Virasami, A; Fairchild, AR; Avery, A; Chalker, J; Kristiansen, M; Haupfear, K; Dalton, JD; Orisme, W; Wen, J; Hubank, M; Kurian, KM; Rowe, C; Maybury, M; Crosier, S; Knipstein, J; Schüller, U; Kordes, U; Kram, DE; Snuderl, M; Bridges, L; Martin, AJ; Doey, LJ; Al-Sarraj, S; Chandler, C; Zebian, B; Cairns, C; Natrajan, R; Boult, JKR; Robinson, SP; Sill, M; Dunkel, IJ; Gilheeney, SW; Rosenblum, MK; Hughes, D; Proszek, PZ; Macdonald, TJ; Preusser, M; Haberler, C; Slavc, I; Packer, R; Ng, H-K; Caspi, S; Popović, M; Faganel Kotnik, B; Wood, MD; Baird, L; Davare, MA; Solomon, DA; Olsen, TK; Brandal, P; Farrell, M; Cryan, JB; Capra, M; Karremann, M; Schittenhelm, J; Schuhmann, MU; Ebinger, M; Dinjens, WNM; Kerl, K; Hettmer, S; Pietsch, T; Andreiuolo, F; Driever, PH; Korshunov, A; Hiddingh, L; Worst, BC; Sturm, D; Zuckermann, M; Witt, O; Bloom, T; Mitchell, C; Miele, E; Colafati, GS; Diomedi-Camassei, F; Bailey, S; Moore, AS; Hassall, TEG; Lowis, SP; Tsoli, M; Cowley, MJ; Ziegler, DS; Karajannis, MA; Aquilina, K; Hargrave, DR; Carceller, F; Marshall, LV; von Deimling, A; Kramm, CM; Pfister, SM; Sahm, F; Baker, SJ; Mastronuzzi, A; Carai, A; Vinci, M; Capper, D; Popov, S; Ellison, DW; Jacques, TS; Jones, DTW; Jones, C (2020-07)
      Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases ...
    • Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. 

      Ng, CKY; Martelotto, LG; Gauthier, A; Wen, H-C; Piscuoglio, S; Lim, RS; Cowell, CF; Wilkerson, PM; Wai, P; Rodrigues, DN; Arnould, L; Geyer, FC; Bromberg, SE; Lacroix-Triki, M; Penault-Llorca, F; Giard, S; Sastre-Garau, X; Natrajan, R; Norton, L; Cottu, PH; Weigelt, B; Vincent-Salomon, A; Reis-Filho, JS (2015-05-22)
      Background HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous ...
    • Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines. 

      Campbell, J; Ryan, CJ; Brough, R; Bajrami, I; Pemberton, HN; Chong, IY; Costa-Cabral, S; Frankum, J; Gulati, A; Holme, H; Miller, R; Postel-Vinay, S; Rafiq, R; Wei, W; Williamson, CT; Quigley, DA; Tym, J; Al-Lazikani, B; Fenton, T; Natrajan, R; Strauss, SJ; Ashworth, A; Lord, CJ (2016-03-03)
      One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase ...
    • Longitudinal analysis of a secondary BRCA2 mutation using digital droplet PCR. 

      Khalique, S; Pettitt, SJ; Kelly, G; Tunariu, N; Natrajan, R; Banerjee, S; Lord, CJ (2020-01)
      Development of resistance to platinum and poly(ADP-ribose) polymerase inhibitors via secondary BRCA gene mutations that restore functional homologous recombination has been observed in a number of cancer types. Here we ...
    • Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis. 

      Natrajan, R; Sailem, H; Mardakheh, FK; Arias Garcia, M; Tape, CJ; Dowsett, M; Bakal, C; Yuan, Y (2016-02-16)
      Background The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed ...
    • A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts. 

      Krasny, L; Bland, P; Burns, J; Lima, NC; Harrison, PT; Pacini, L; Elms, ML; Ning, J; Martinez, VG; Yu, Y-R; Acton, SE; Ho, P-C; Calvo, F; Swain, A; Howard, BA; Natrajan, RC; Huang, PH (2020-07-14)
      SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that ...
    • Multifaceted dysregulation of the epidermal growth factor receptor pathway in clear cell sarcoma of the kidney. 

      Little, SE; Bax, DA; Rodriguez-Pinilla, M; Natrajan, R; Messahel, B; Pritchard-Jones, K; Vujanic, GM; Reis-Filho, JS; Jones, C (2007-08)
      Purpose Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase overexpressed in a variety of human malignancies, against which targeted therapies have shown efficacy in lung and brain tumors. Clinical responses ...
    • Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers. 

      Khalique, S; Naidoo, K; Attygalle, AD; Kriplani, D; Daley, F; Lowe, A; Campbell, J; Jones, T; Hubank, M; Fenwick, K; Matthews, N; Rust, AG; Lord, CJ; Banerjee, S; Natrajan, R (2018-07-20)
      ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ...
    • Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. 

      Yap, TA; O'Carrigan, B; Penney, MS; Lim, JS; Brown, JS; de Miguel Luken, MJ; Tunariu, N; Perez-Lopez, R; Rodrigues, DN; Riisnaes, R; Figueiredo, I; Carreira, S; Hare, B; McDermott, K; Khalique, S; Williamson, CT; Natrajan, R; Pettitt, SJ; Lord, CJ; Banerji, U; Pollard, J; Lopez, J; de Bono, JS (2020-09)
      Purpose Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ...