Now showing items 1-15 of 15

    • Between-region genetic divergence reflects the mode and tempo of tumor evolution. 

      Sun, R; Hu, Z; Sottoriva, A; Graham, TA; Harpak, A; Ma, Z; Fischer, JM; Shibata, D; Curtis, C (2017-07)
      Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural ...
    • 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 ...
    • FFPE breast tumour blocks provide reliable sources of both germline and malignant DNA for investigation of genetic determinants of individual tumour responses to treatment. 

      Wilkins, A; Chauhan, R; Rust, A; Pearson, A; Daley, F; Manodoro, F; Fenwick, K; Bliss, J; Yarnold, J; Somaiah, N (2018-08)
      BACKGROUND:Bio-banked formalin-fixed paraffin-embedded (FFPE) tissues provide an excellent opportunity for translational genomic research. Historically matched blood has not always been collected as a source of germline ...
    • Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. 

      Turajlic, S; Litchfield, K; Xu, H; Rosenthal, R; McGranahan, N; Reading, JL; Wong, YNS; Rowan, A; Kanu, N; Al Bakir, M; Chambers, T; Salgado, R; Savas, P; Loi, S; Birkbak, NJ; Sansregret, L; Gore, M; Larkin, J; Quezada, SA; Swanton, C (2017-08)
      The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift ...
    • Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. 

      Mackay, A; Burford, A; Carvalho, D; Izquierdo, E; Fazal-Salom, J; Taylor, KR; Bjerke, L; Clarke, M; Vinci, M; Nandhabalan, M; Temelso, S; Popov, S; Molinari, V; Raman, P; Waanders, AJ; Han, HJ; Gupta, S; Marshall, L; Zacharoulis, S; Vaidya, S; Mandeville, HC; Bridges, LR; Martin, AJ; Al-Sarraj, S; Chandler, C; Ng, H-K; Li, X; Mu, K; Trabelsi, S; Brahim, DH-B; Kisljakov, AN; Konovalov, DM; Moore, AS; Carcaboso, AM; Sunol, M; de Torres, C; Cruz, O; Mora, J; Shats, LI; Stavale, JN; Bidinotto, LT; Reis, RM; Entz-Werle, N; Farrell, M; Cryan, J; Crimmins, D; Caird, J; Pears, J; Monje, M; Debily, M-A; Castel, D; Grill, J; Hawkins, C; Nikbakht, H; Jabado, N; Baker, SJ; Pfister, SM; Jones, DTW; Fouladi, M; von Bueren, AO; Baudis, M; Resnick, A; Jones, C (2017-10-09)
      We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating ...
    • Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. 

      Mackay, A; Burford, A; Carvalho, D; Izquierdo, E; Fazal-Salom, J; Taylor, KR; Bjerke, L; Clarke, M; Vinci, M; Nandhabalan, M; Temelso, S; Popov, S; Molinari, V; Raman, P; Waanders, AJ; Han, HJ; Gupta, S; Marshall, L; Zacharoulis, S; Vaidya, S; Mandeville, HC; Bridges, LR; Martin, AJ; Al-Sarraj, S; Chandler, C; Ng, H-K; Li, X; Mu, K; Trabelsi, S; Brahim, DH-B; Kisljakov, AN; Konovalov, DM; Moore, AS; Carcaboso, AM; Sunol, M; de Torres, C; Cruz, O; Mora, J; Shats, LI; Stavale, JN; Bidinotto, LT; Reis, RM; Entz-Werle, N; Farrell, M; Cryan, J; Crimmins, D; Caird, J; Pears, J; Monje, M; Debily, M-A; Castel, D; Grill, J; Hawkins, C; Nikbakht, H; Jabado, N; Baker, SJ; Pfister, SM; Jones, DTW; Fouladi, M; von Bueren, AO; Baudis, M; Resnick, A; Jones, C (2017-10-09)
      We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating ...
    • Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. 

      Mackay, A; Burford, A; Carvalho, D; Izquierdo, E; Fazal-Salom, J; Taylor, KR; Bjerke, L; Clarke, M; Vinci, M; Nandhabalan, M; Temelso, S; Popov, S; Molinari, V; Raman, P; Waanders, AJ; Han, HJ; Gupta, S; Marshall, L; Zacharoulis, S; Vaidya, S; Mandeville, HC; Bridges, LR; Martin, AJ; Al-Sarraj, S; Chandler, C; Ng, H-K; Li, X; Mu, K; Trabelsi, S; Brahim, DH-B; Kisljakov, AN; Konovalov, DM; Moore, AS; Carcaboso, AM; Sunol, M; de Torres, C; Cruz, O; Mora, J; Shats, LI; Stavale, JN; Bidinotto, LT; Reis, RM; Entz-Werle, N; Farrell, M; Cryan, J; Crimmins, D; Caird, J; Pears, J; Monje, M; Debily, M-A; Castel, D; Grill, J; Hawkins, C; Nikbakht, H; Jabado, N; Baker, SJ; Pfister, SM; Jones, DTW; Fouladi, M; von Bueren, AO; Baudis, M; Resnick, A; Jones, C (2017-10)
      We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating ...
    • Neutral tumor evolution in myeloma is associated with poor prognosis. 

      Johnson, DC; Lenive, O; Mitchell, J; Jackson, G; Owen, R; Drayson, M; Cook, G; Jones, JR; Pawlyn, C; Davies, FE; Walker, BA; Wardell, C; Gregory, WM; Cairns, D; Morgan, GJ; Houlston, RS; Houlston, RS; Kaiser, MF (2017-10)
      Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, ...
    • De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of the Mediator Complex, Cause a Syndromic Developmental Disorder. 

      Calpena, E; Hervieu, A; Kaserer, T; Swagemakers, SMA; Goos, JAC; Popoola, O; Ortiz-Ruiz, MJ; Barbaro-Dieber, T; Bownass, L; Brilstra, EH; Brimble, E; Foulds, N; Grebe, TA; Harder, AVE; Lees, MM; Monaghan, KG; Newbury-Ecob, RA; Ong, K-R; Osio, D; Reynoso Santos, FJ; Ruzhnikov, MRZ; Telegrafi, A; van Binsbergen, E; van Dooren, MF; Deciphering Developmental Disorders Study; van der Spek, PJ; Blagg, J; Twigg, SRF; Mathijssen, IMJ; Clarke, PA; Wilkie, AOM (2019-04)
      The Mediator is an evolutionarily conserved, multi-subunit complex that regulates multiple steps of transcription. Mediator activity is regulated by the reversible association of a four-subunit module comprising CDK8 or ...
    • De novo mutations implicate novel genes in systemic lupus erythematosus. 

      Pullabhatla, V; Roberts, AL; Lewis, MJ; Mauro, D; Morris, DL; Odhams, CA; Tombleson, P; Liljedahl, U; Vyse, S; Simpson, MA; Sauer, S; de Rinaldis, E; Syvänen, A-C; Vyse, TJ (2018-02)
      The omnigenic model of complex disease stipulates that the majority of the heritability will be explained by the effects of common variation on genes in the periphery of core disease pathways. Rare variant associations, ...
    • Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. 

      Chubb, D; Broderick, P; Dobbins, SE; Frampton, M; Kinnersley, B; Penegar, S; Price, A; Ma, YP; Sherborne, AL; Palles, C; Timofeeva, MN; Bishop, DT; Dunlop, MG; Tomlinson, I; Houlston, RS (2016-06-22)
      Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enshrined in high-impact rare alleles, which are mechanistically and clinically important. ...
    • REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. 

      Ioannidis, NM; Rothstein, JH; Pejaver, V; Middha, S; McDonnell, SK; Baheti, S; Musolf, A; Li, Q; Holzinger, E; Karyadi, D; Cannon-Albright, LA; Teerlink, CC; Stanford, JL; Isaacs, WB; Xu, J; Cooney, KA; Lange, EM; Schleutker, J; Carpten, JD; Powell, IJ; Cussenot, O; Cancel-Tassin, G; Giles, GG; MacInnis, RJ; Maier, C; Hsieh, C-L; Wiklund, F; Catalona, WJ; Foulkes, WD; Mandal, D; Eeles, RA; Kote-Jarai, Z; Bustamante, CD; Schaid, DJ; Hastie, T; Ostrander, EA; Bailey-Wilson, JE; Radivojac, P; Thibodeau, SN; Whittemore, AS; Sieh, W (2016-10)
      The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the ...
    • The Spectrum and Clinical Impact of Epigenetic Modifier Mutations in Myeloma. 

      Pawlyn, C; Kaiser, MF; Heuck, C; Melchor, L; Wardell, CP; Murison, A; Chavan, SS; Johnson, DC; Begum, DB; Dahir, NM; Proszek, PZ; Cairns, DA; Boyle, EM; Jones, JR; Cook, G; Drayson, MT; Owen, RG; Gregory, WM; Jackson, GH; Barlogie, B; Davies, FE; Walker, BA; Morgan, GJ (2016-12)
      Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike other B-cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been reported previously. ...
    • Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model. 

      Maguire, SL; Peck, B; Wai, PT; Campbell, J; Barker, H; Gulati, A; Daley, F; Vyse, S; Huang, P; Lord, CJ; Farnie, G; Brennan, K; Natrajan, R (2016-11)
      The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations ...
    • Tracking the Evolution of Non-Small-Cell Lung Cancer. 

      Jamal-Hanjani, M; Wilson, GA; McGranahan, N; Birkbak, NJ; Watkins, TBK; Veeriah, S; Shafi, S; Johnson, DH; Mitter, R; Rosenthal, R; Salm, M; Horswell, S; Escudero, M; Matthews, N; Rowan, A; Chambers, T; Moore, DA; Turajlic, S; Xu, H; Lee, S-M; Forster, MD; Ahmad, T; Hiley, CT; Abbosh, C; Falzon, M; Borg, E; Marafioti, T; Lawrence, D; Hayward, M; Kolvekar, S; Panagiotopoulos, N; Janes, SM; Thakrar, R; Ahmed, A; Blackhall, F; Summers, Y; Shah, R; Joseph, L; Quinn, AM; Crosbie, PA; Naidu, B; Middleton, G; Langman, G; Trotter, S; Nicolson, M; Remmen, H; Kerr, K; Chetty, M; Gomersall, L; Fennell, DA; Nakas, A; Rathinam, S; Anand, G; Khan, S; Russell, P; Ezhil, V; Ismail, B; Irvin-Sellers, M; Prakash, V; Lester, JF; Kornaszewska, M; Attanoos, R; Adams, H; Davies, H; Dentro, S; Taniere, P; O'Sullivan, B; Lowe, HL; Hartley, JA; Iles, N; Bell, H; Ngai, Y; Shaw, JA; Herrero, J; Szallasi, Z; Schwarz, RF; Stewart, A; Quezada, SA; Le Quesne, J; Van Loo, P; Dive, C; Hackshaw, A; Swanton, C; TRACERx Consortium (2017-06)
      BACKGROUND:Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate ...