Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
| Title: | Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features |
|---|---|
| Authors: | 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; 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; Houlston RS; Martin-Subero JI; Schuh A |
| Source: | Nature Genetics, November 2022 |
| Publisher Information: | Springer Nature |
| Publication Year: | 2022 |
| Collection: | Newcastle University Library ePrints Service |
| Description: | © 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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | unknown |
| Relation: | https://eprints.ncl.ac.uk/287937; https://eprints.ncl.ac.uk/fulltext.aspx?url=287937/9ADE9DBF-51C6-4699-AC7C-ED1D492723D3.pdf&pub_id=287937 |
| Availability: | https://eprints.ncl.ac.uk/287937 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.4E4560F2 |
| Database: | BASE |