Mutations driving CLL and their evolution in progression and relapse
By D. Landau, E. Tausch, A. Taylor-Weiner, Chip Stewart, Johannes G. Reiter, J. Bahlo, S. Kluth, I. Bozic, Mike S. Lawrence, S. Böttcher and 21 more. Nature, 2015
1,030 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Genetics
View Paper: https://www.semanticscholar.org/paper/2dd4441d771b441149dd05555e719d5ab072dcf3
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Citations in the corpus
- Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab (2017, background): “…has been reported following other cancer therapies such as cytotoxic treatments in glioblastoma (GBM) and chronic lymphocytic leukemia, and our observation of CDKN2A loss in four patients with PD agrees with reported changes in GBM tumors at progression (Johnson et al., 2014; Landau et al., 2015).”