Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.
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ICR Authors
Authors
Robbe, P
Ridout, KE
Vavoulis, DV
Dréau, H
Kinnersley, B
Denny, N
Chubb, D
Appleby, N
Cutts, A
Cornish, AJ
Lopez-Pascua, L
Clifford, R
Burns, A
Stamatopoulos, B
Cabes, M
Alsolami, R
Antoniou, P
Oates, M
Cavalieri, D
Genomics England Research Consortium,
CLL pilot consortium,
Gibson, J
Prabhu, AV
Schwessinger, R
Jennings, D
James, T
Maheswari, U
Duran-Ferrer, M
Carninci, P
Knight, SJL
Månsson, R
Hughes, J
Davies, J
Ross, M
Bentley, D
Strefford, JC
Devereux, S
Pettitt, AR
Hillmen, P
Caulfield, MJ
Houlston, RS
Martín-Subero, JI
Schuh, A
Ridout, KE
Vavoulis, DV
Dréau, H
Kinnersley, B
Denny, N
Chubb, D
Appleby, N
Cutts, A
Cornish, AJ
Lopez-Pascua, L
Clifford, R
Burns, A
Stamatopoulos, B
Cabes, M
Alsolami, R
Antoniou, P
Oates, M
Cavalieri, D
Genomics England Research Consortium,
CLL pilot consortium,
Gibson, J
Prabhu, AV
Schwessinger, R
Jennings, D
James, T
Maheswari, U
Duran-Ferrer, M
Carninci, P
Knight, SJL
Månsson, R
Hughes, J
Davies, J
Ross, M
Bentley, D
Strefford, JC
Devereux, S
Pettitt, AR
Hillmen, P
Caulfield, MJ
Houlston, RS
Martín-Subero, JI
Schuh, A
Document Type
Journal Article
Date
2022-11-01
Date Accepted
2022-09-16
Abstract
The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.
Citation
Nature Genetics, 2022, 54 (11), pp. 1675 - 1689
Source Title
Nature Genetics
Publisher
NATURE PORTFOLIO
ISSN
1061-4036
eISSN
1546-1718
1546-1718
1546-1718
Collections
Research Team
Cancer Genomics