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

Robbe, Pauline; Ridout, Kate E; Vavoulis, Dimitrios V; Dréau, Helene; Kinnersley, Ben; Denny, Nicholas; Chubb, Daniel; ... Schuh, Anna; + view all (2022) Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features. Nature Genetics , 54 pp. 1675-1689. 10.1038/s41588-022-01211-y. Green open access

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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.

Type: Article
Title: Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-022-01211-y
Publisher version: https://doi.org/10.1038/s41588-022-01211-y
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Chronic lymphocytic leukaemia, Genomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10159378
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