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Lookup NU author(s): Professor James AllanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). 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.
Author(s): Robbe P, Ridout KE, Dreau 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, Ambrose JC, Arumugam P, Bevers R, Bleda M, Boardman-Pretty F, Boustred CR, Brittain H, Brown MA, Caulfield MJ, Chan GC, Fowler T, Giess A, Hamblin A, Henderson S, Hubbard TJP, Jackson R, Jones LJ, Kasperaviciute D, Kayikci M, Kousathanas A, Lahnstein L, Leigh SEA, Leong IUS, Lopez FJ, Maleady-Crowe F, McEntagart M, Minneci F, Moutsianas L, Mueller M, Murugaesu N, Need AC, O'Donovan P, Odhams CA, Patch C, Perez-Gil D, Pereira MB, Pullinger J, Rahim T, Rendon A, Rogers T, Savage K, Sawant K, Scott RH, Siddiq A, Sieghart A, Smith SC, Sosinsky A, Stuckey A, Tanguy M, Taylor Tavares AL, Thomas ERA, Thompson SR, Tucci A, Welland MJ, Williams E, Witkowska K, Wood SM, Allan J, Bisshopp G, Blakemore S, Boultwood J, Bruce D, Buffa F, Buggins A, Cohen G, Cwynarski K, Dearden C, Dillon R, Ennis S, Falciani F, Follows G, Forconi F, Forster J, Fox C, Gribben J, Hockaday A, Howard D, Jackson A, Kalakonda N, Khan U, Law P, Lefevre P, Lin K, Maseno S, Moss P, Packham G, Palles C, Parker H, Patten P, Pellagatti A, Pratt G, Ramsay A, Rawstron A, Rose-Zerilli M, Slupsky J, Stankovic T, Steele A, Strefford J, Varadarajan S, Vavoulis DV, Vavoulis DV, Wagner S, Westhead D, Wordsworth S, Zhuang J, Gibson J, Prabhu AV, Schwessinger R, Jennings D, James T, Maheswari U, Duran-Ferrer M, Carninci P, Knight SJL, Mansson R, Hughes J, Davies J, Ross M, Bentley D, Strefford JC, Devereux S, Pettitt AR, Hillmen P, Caulfield MJ, Houlston RS, Martin-Subero JI, Schuh A
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2022
Volume: 54
Issue: 11
Pages: 1675-1689
Online publication date: 04/11/2022
Acceptance date: 16/09/2022
Date deposited: 03/09/2025
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41588-022-01211-y
DOI: 10.1038/s41588-022-01211-y
Data Access Statement: The National Genomic Research Library (NGRL) is a ‘reading library’, therefore data cannot be extracted directly. All WGS data, BAM files and processed files cited can be viewed in situ via the Haematological Malignancy Genomics England Clinical Interpretation Partnership (GECIP), once an individual’s data access has been approved. The link to becoming a member of GECIP to get access can be found here https://www.genomicsengland.co.uk/research/academic/join-gecip. The process involves an online application, verification by the applicant’s institution, completion of a short information governance training course (circa 30 min), and verification of approval by the Haematological Malignancy domain lead (A.S., see contact details for corresponding author). Please see https://www.genomicsengland.co.uk/research/academic for more information. [See the article for the full Data Availability Statement.]
PubMed id: 36333502
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