Mutations driving CLL and their evolution in progression and relapse
Name
Lander_Mutations driving.pdf
Size
4.9 MB
Format
Adobe PDF
Checksum (MD5)
c2165b73eda207d4e2ac8bae43ebb9d6
Author(s)
Lander, Eric Steven
Date Issued
October 2015
Journal
Nature
Publisher
Nature Publishing Group
Citation
Landau, Dan A. et al. “Mutations Driving CLL and Their Evolution in Progression and Relapse.” Nature 526.7574 (2015): 525–530.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/nature15395
