Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
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Landau D, Tausch E, Taylor Weiner A, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526(7574):525-530. doi:10.1038/nature15395
Landau, D., Tausch, E., Taylor Weiner, A., Stewart, C., Reiter, J., Bahlo, J., … Wu, C. (2015). Mutations driving CLL and their evolution in progression and relapse. Nature, 526(7574), 525–530. https://doi.org/10.1038/nature15395
Landau, Dan, Eugen Tausch, Amaro Taylor Weiner, Chip Stewart, Johannes Reiter, Jasmin Bahlo, Sandra Kluth, et al. “Mutations Driving CLL and Their Evolution in Progression and Relapse.” Nature 526, no. 7574 (2015): 525–30. https://doi.org/10.1038/nature15395.
D. Landau et al., “Mutations driving CLL and their evolution in progression and relapse,” Nature, vol. 526, no. 7574, pp. 525–530, 2015.
Landau D, Tausch E, Taylor Weiner A, Stewart C, Reiter J, Bahlo J, Kluth S, Božić I, Lawrence M, Böttcher S, Carter S, Cibulskis K, Mertens D, Sougnez C, Rosenberg M, Hess J, Edelmann J, Kless S, Kneba M, Ritgen M, Fink A, Fischer K, Gabriel S, Lander E, Nowak M, Döhner H, Hallek M, Neuberg D, Getz G, Stilgenbauer S, Wu C. 2015. Mutations driving CLL and their evolution in progression and relapse. Nature. 526(7574), 525–530.
Landau, Dan, et al. “Mutations Driving CLL and Their Evolution in Progression and Relapse.” Nature, vol. 526, no. 7574, Nature Publishing Group, 2015, pp. 525–30, doi:10.1038/nature15395.