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

Pauline Robbe; Kate E Ridout; Dimitrios V Vavoulis; Helene Dréau; Ben Kinnersley; Nicholas Denny; Daniel Chubb; Niamh Appleby; Anthony Cutts; Alex J Cornish; Laura Lopez-Pascua; Ruth Clifford; Adam Burns; Basile Stamatopoulos; Maite Cabes; Reem Alsolami; Pavlos Antoniou; Melanie Oates; Doriane Cavalieri; Jane Gibson; Anika V Prabhu; Ron Schwessinger; Daisy Jennings; Terena James; Uma Maheswari; Martí Duran-Ferrer; Piero Carninci; Samantha J L Knight; Robert Månsson; Jim Hughes; James Davies; Mark Ross; David Bentley; Jonathan C Strefford; Stephen Devereux; Andrew R Pettitt; Peter Hillmen; Mark J Caulfield; Richard S Houlston; José I Martín-Subero; Anna Schuh; Genomics England Research Consortium

doi:10.1038/s41588-022-01211-y

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

Journal article

Open access

Peer reviewed

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

Pauline Robbe, Kate E Ridout, Dimitrios V Vavoulis, Helene Dréau, Ben Kinnersley, Nicholas Denny, Daniel Chubb, Niamh Appleby, Anthony Cutts, Alex J Cornish, …

Nature genetics, Vol.54(11), pp.1675-1689

01/11/2022

DOI: https://doi.org/10.1038/s41588-022-01211-y

PMID: 36333502

Abstract

Genomics

Humans

Leukemia, Lymphocytic, Chronic, B-Cell - genetics

Mutation

Prognosis

Whole Genome Sequencing

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.

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Title: Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
Creators - without role: Pauline Robbe - University of Oxford
Kate E Ridout - University of Oxford
Dimitrios V Vavoulis - University of Oxford
Helene Dréau - University of Oxford
Ben Kinnersley - Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK
Nicholas Denny - University of Oxford
Daniel Chubb - Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK
Niamh Appleby - University of Oxford
Anthony Cutts - University of Oxford
Alex J Cornish - Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK
Laura Lopez-Pascua - UK Health Security Agency
Ruth Clifford - University of Limerick
Adam Burns - University of Oxford
Basile Stamatopoulos - Université Libre de Bruxelles
Maite Cabes - Oxford University Hospitals NHS Trust
Reem Alsolami - King Abdulaziz University
Pavlos Antoniou - Illumina Cambridge Ltd., Cambridge, UK
Melanie Oates - University of Liverpool
Doriane Cavalieri - Department of Haematology, CHU de Clermont-Ferrand, Clermont-Ferrand, France
Jane Gibson - University of Southampton
Anika V Prabhu - RIKEN Center for Integrative Medical Sciences
Ron Schwessinger - University of Oxford
Daisy Jennings - RIKEN Center for Integrative Medical Sciences
Terena James - Illumina Cambridge Ltd., Cambridge, UK
Uma Maheswari - Illumina Cambridge Ltd., Cambridge, UK
Martí Duran-Ferrer - Universitat de Barcelona
Piero Carninci - Human Technopole
Samantha J L Knight - Oxford University Clinical Academic Graduate School, University of Oxford Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
Robert Månsson - Karolinska Institutet
Jim Hughes - University of Oxford
James Davies - University of Oxford
Mark Ross - Illumina
David Bentley - Illumina
Jonathan C Strefford - University of Southampton
Stephen Devereux - Kings College London, London, UK
Andrew R Pettitt - Clatterbridge Cancer Centre NHS Foundation Trust
Peter Hillmen - St James's University Hospital
Mark J Caulfield - Queen Mary University of London
Richard S Houlston - Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK
José I Martín-Subero - Institució Catalana de Recerca i Estudis Avançats
Anna Schuh - University of Oxford
Genomics England Research Consortium
Publication Details: Nature genetics, Vol.54(11), pp.1675-1689
Grant note: C124388 / Cancer Research UK MC_PC_14089 / Medical Research Council MC_UU_00029/4 / Medical Research Council Department of Health MR/M009203/1 / Medical Research Council C24563/A15581 / Cancer Research UK MC_EX_MR/M009203/1 / Medical Research Council MR/R008108/1 / Medical Research Council C42023/A29370 / Cancer Research UK C2750/A23669 / Cancer Research UK C34999/A18087 / Cancer Research UK 214388 / Wellcome Trust
Identifiers: 9939784208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article