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Mutations driving CLL and their evolution in progression and relapse.
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- معلومة اضافية
- المصدر:
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
- بيانات النشر:
Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
- الموضوع:
Disease Progression* ;
Evolution, Molecular*;
Leukemia, Lymphocytic, Chronic, B-Cell/
*genetics ;
Mutation/
*genetics ;
Neoplasm Recurrence, Local/
*genetics;
Cell Transformation, Neoplastic/
genetics ;
Clone Cells/
metabolism ;
Clone Cells/
pathology ;
DNA Copy Number Variations/
genetics ;
Exome/
genetics ;
Genes, myc/
genetics ;
Humans ;
Ikaros Transcription Factor/
genetics ;
Leukemia, Lymphocytic, Chronic, B-Cell/
diagnosis ;
Leukemia, Lymphocytic, Chronic, B-Cell/
pathology ;
Leukemia, Lymphocytic, Chronic, B-Cell/
therapy ;
MAP Kinase Signaling System/
genetics ;
Prognosis ;
RNA Processing, Post-Transcriptional/
genetics ;
RNA Transport/
genetics ;
Ribosomal Proteins/
genetics ;
Treatment Outcome - نبذة مختصرة :
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.
- Comments:
Comment in: Cell Death Dis. 2016;7:e2042. (PMID: 26775696)
- References:
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- Grant Information:
U10 CA180861 United States CA NCI NIH HHS; 1U10CA180861-01 United States CA NCI NIH HHS; R01 CA182461 United States CA NCI NIH HHS; U54 HG003067 United States HG NHGRI NIH HHS; 1K01ES025431-01 United States ES NIEHS NIH HHS; 1R01CA182461-02 United States CA NCI NIH HHS; U54HG003067 United States HG NHGRI NIH HHS; K01 ES025431 United States ES NIEHS NIH HHS; P01 CA081534 United States CA NCI NIH HHS; 1R01CA184922-01 United States CA NCI NIH HHS; R01 CA184922 United States CA NCI NIH HHS; R01 HL116452 United States HL NHLBI NIH HHS
- Molecular Sequence:
dbGaP PHS000922.V1.P1
- الرقم المعرف:
0 (IKZF3 protein, human)
0 (Ribosomal Proteins)
0 (ribosomal protein S21)
148971-36-2 (Ikaros Transcription Factor)
- الموضوع:
Date Created: 20151016 Date Completed: 20151117 Latest Revision: 20220317
- الموضوع:
20221213
- الرقم المعرف:
PMC4815041
- الرقم المعرف:
10.1038/nature15395
- الرقم المعرف:
26466571
No Comments.