Landau, Dan A., Tausch, Eugen, Taylor-Weiner, Amaro N., Stewart, Chip, Reiter, Johannes G. ORCID: 0000-0002-0170-7353, Bahlo, Jasmin, Kluth, Sandra, Bozic, Ivana ORCID: 0000-0003-2761-825X, Lawrence, Mike, Boettcher, Sebastian, Carter, Scott L., Cibulskis, Kristian, Mertens, Daniel ORCID: 0000-0003-0227-7188, Sougnez, Carrie L., Rosenberg, Mara ORCID: 0000-0001-6400-3161, Hess, Julian M., Edelmann, Jennifer, Kless, Sabrina, Kneba, Michael, Ritgen, Matthias, Fink, Anna, Fischer, Kirsten, Gabriel, Stacey, Lander, Eric S., Nowak, Martin A., Doehner, Hartmut, Hallek, Michael, Neuberg, Donna, Getz, Gad, Stilgenbauer, Stephan and Wu, Catherine J. (2015). Mutations driving CLL and their evolution in progression and relapse. Nature, 526 (7574). S. 525 - 542. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Landau, Dan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor-Weiner, Amaro N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewart, ChipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiter, Johannes G.UNSPECIFIEDorcid.org/0000-0002-0170-7353UNSPECIFIED
Bahlo, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluth, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bozic, IvanaUNSPECIFIEDorcid.org/0000-0003-2761-825XUNSPECIFIED
Lawrence, MikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boettcher, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carter, Scott L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cibulskis, KristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mertens, DanielUNSPECIFIEDorcid.org/0000-0003-0227-7188UNSPECIFIED
Sougnez, Carrie L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenberg, MaraUNSPECIFIEDorcid.org/0000-0001-6400-3161UNSPECIFIED
Hess, Julian M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edelmann, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kless, SabrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneba, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ritgen, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabriel, StaceyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lander, Eric S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nowak, Martin A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doehner, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuberg, DonnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Getz, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Catherine J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-389452
DOI: 10.1038/nature15395
Journal or Publication Title: Nature
Volume: 526
Number: 7574
Page Range: S. 525 - 542
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; BRAF MUTATIONS; CANCER; HETEROGENEITY; REVEALS; DRIVER; MYCMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38945

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item