Mutations driving CLL and their evolution in progression and relapse
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 le...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/106816 |
| _version_ | 1826212491997216768 |
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| author | Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven |
| author_sort | Lander, Eric Steven |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:23:07Z |
| format | Article |
| id | mit-1721.1/106816 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:23:07Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1068162022-10-02T02:34:11Z Mutations driving CLL and their evolution in progression and relapse Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven 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. National Human Genome Research Institute (U.S.) (Grant U54HG003067) 2017-01-31T19:33:45Z 2017-01-31T19:33:45Z 2015-10 2015-03 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/106816 Landau, Dan A. et al. “Mutations Driving CLL and Their Evolution in Progression and Relapse.” Nature 526.7574 (2015): 525–530. en_US http://dx.doi.org/10.1038/nature15395 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Lander, Eric Steven Mutations driving CLL and their evolution in progression and relapse |
| title | Mutations driving CLL and their evolution in progression and relapse |
| title_full | Mutations driving CLL and their evolution in progression and relapse |
| title_fullStr | Mutations driving CLL and their evolution in progression and relapse |
| title_full_unstemmed | Mutations driving CLL and their evolution in progression and relapse |
| title_short | Mutations driving CLL and their evolution in progression and relapse |
| title_sort | mutations driving cll and their evolution in progression and relapse |
| url | http://hdl.handle.net/1721.1/106816 |
| work_keys_str_mv | AT landerericsteven mutationsdrivingcllandtheirevolutioninprogressionandrelapse |