Now showing items 1-11 of 11

    • A streamlined workflow for single-cells genome-wide copy-number profiling by low-pass sequencing of LM-PCR whole-genome amplification products. 

      Ferrarini, A; Forcato, C; Buson, G; Tononi, P; Del Monaco, V; Terracciano, M; Bolognesi, C; Fontana, F; Medoro, G; Neves, R; Möhlendick, B; Rihawi, K; Ardizzoni, A; Sumanasuriya, S; Flohr, P; Lambros, M; de Bono, J; Stoecklein, NH; Manaresi, N (2018-01)
      Chromosomal instability and associated chromosomal aberrations are hallmarks of cancer and play a critical role in disease progression and development of resistance to drugs. Single-cell genome analysis has gained interest ...
    • 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 ...
    • Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer. 

      Chopra, N; Tovey, H; Pearson, A; Cutts, R; Toms, C; Proszek, P; Hubank, M; Dowsett, M; Dodson, A; Daley, F; Kriplani, D; Gevensleben, H; Davies, HR; Degasperi, A; Roylance, R; Chan, S; Tutt, A; Skene, A; Evans, A; Bliss, JM; Nik-Zainal, S; Turner, NC (2020-05-29)
      Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO ...
    • Identification of recurrent noncoding mutations in B-cell lymphoma using capture Hi-C. 

      Cornish, AJ; Hoang, PH; Dobbins, SE; Law, PJ; Chubb, D; Orlando, G; Houlston, RS (2019-01)
      The identification of driver mutations is fundamental to understanding oncogenesis. Although genes frequently mutated in B-cell lymphoma have been identified, the search for driver mutations has largely focused on the ...
    • Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. 

      Zhang, AW; McPherson, A; Milne, K; Kroeger, DR; Hamilton, PT; Miranda, A; Funnell, T; Little, N; de Souza, CPE; Laan, S; LeDoux, S; Cochrane, DR; Lim, JLP; Yang, W; Roth, A; Smith, MA; Ho, J; Tse, K; Zeng, T; Shlafman, I; Mayo, MR; Moore, R; Failmezger, H; Heindl, A; Wang, YK; Bashashati, A; Grewal, DS; Brown, SD; Lai, D; Wan, ANC; Nielsen, CB; Huebner, C; Tessier-Cloutier, B; Anglesio, MS; Bouchard-Côté, A; Yuan, Y; Wasserman, WW; Gilks, CB; Karnezis, AN; Aparicio, S; McAlpine, JN; Huntsman, DG; Holt, RA; Nelson, BH; Shah, SP (2018-06)
      High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape ...
    • Measuring single cell divisions in human tissues from multi-region sequencing data. 

      Werner, B; Case, J; Williams, MJ; Chkhaidze, K; Temko, D; Fernández-Mateos, J; Cresswell, GD; Nichol, D; Cross, W; Spiteri, I; Huang, W; Tomlinson, IPM; Barnes, CP; Graham, TA; Sottoriva, A (2020-02-25)
      Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ...
    • Mutational processes contributing to the development of multiple myeloma. 

      Hoang, PH; Cornish, AJ; Dobbins, SE; Kaiser, M; Houlston, RS (2019-08-06)
      To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are ...
    • RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer. 

      Nava Rodrigues, D; Casiraghi, N; Romanel, A; Crespo, M; Miranda, S; Rescigno, P; Figueiredo, I; Riisnaes, R; Carreira, S; Sumanasuriya, S; Gasperini, P; Sharp, A; Mateo, J; Makay, A; McNair, C; Schiewer, M; Knudsen, K; Boysen, G; Demichelis, F; de Bono, JS (2019-01)
      Purpose Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic heterogeneity ...
    • Subclonal reconstruction of tumors by using machine learning and population genetics. 

      Caravagna, G; Heide, T; Williams, MJ; Zapata, L; Nichol, D; Chkhaidze, K; Cross, W; Cresswell, GD; Werner, B; Acar, A; Chesler, L; Barnes, CP; Sanguinetti, G; Graham, TA; Sottoriva, A (2020-09-02)
      Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ...
    • The MOBSTER R package for tumour subclonal deconvolution from bulk DNA whole-genome sequencing data. 

      Caravagna, G; Sanguinetti, G; Graham, TA; Sottoriva, A (2020-11-17)
      Background The large-scale availability of whole-genome sequencing profiles from bulk DNA sequencing of cancer tissues is fueling the application of evolutionary theory to cancer. From a bulk biopsy, subclonal deconvolution ...
    • Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms. 

      Hoang, PH; Dobbins, SE; Cornish, AJ; Chubb, D; Law, PJ; Kaiser, M; Houlston, RS (2018-11)
      Multiple myeloma (MM) is a biologically heterogeneous malignancy, however, the mechanisms underlying this complexity are incompletely understood. We report an analysis of the whole-genome sequencing of 765 MM patients from ...