Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.

Pauline Robbe, Ridout KE, Dimitris Vavoulis, H Dréau, Ben Kinnersley, Nicholas Denny, D Chubb, Niamh Appleby, A Cutts, Alex J Cornish, L Lopez-Pascua, R Clifford, A Burns, B Stamatopoulos, M Cabes, R Alsolami, P Antoniou, M Oates, D Cavalieri, Genomics England Research ConsortiumCLL pilot consortium, Jane Gibson, Prabhu AV, R Schwessinger, D Jennings, T James, U Maheswari, Martí Duran-Ferrer, P Carninci, Knight SJL, R Månsson, Jim Hughes, Jim Davies, James Davies, M Ross, D Bentley, Jonathan C Strefford, Stephen Devereux, Pettitt AR, P Hillmen, Caulfield MJ, Richard Houlston, Martín-Subero JI, schuh Anna

Research output: Contribution to journalArticlepeer-review

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.
Original languageUndefined/Unknown
Pages (from-to)1675-1689
Number of pages15
JournalNature Genetics
Volume54
Issue number11
DOIs
Publication statusPublished - 4 Nov 2022

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