Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.
Date
2022-11-01Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Whole Genome Sequencing
Mutation
Genomics
Prognosis
Research team
Cancer Genomics
Language
eng
Date accepted
2022-09-16
License start date
2022-11-01
Citation
Nature Genetics, 2022, 54 (11), pp. 1675 - 1689
Publisher
NATURE PORTFOLIO