Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
30
04
2021
accepted:
16
09
2022
pubmed:
6
11
2022
medline:
15
11
2022
entrez:
5
11
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36333502
doi: 10.1038/s41588-022-01211-y
pii: 10.1038/s41588-022-01211-y
pmc: PMC9649442
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1675-1689Subventions
Organisme : Cancer Research UK
ID : C124388
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C42023/A29370
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C24563/A15581
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C2750/A23669
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 23669
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C34999/A18087
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N00969X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Blood Cancer UK
ID : 15047
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 214388
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12362
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R008108/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29370
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00029/4
Pays : United Kingdom
Investigateurs
J C Ambrose
(JC)
P Arumugam
(P)
R Bevers
(R)
M Bleda
(M)
F Boardman-Pretty
(F)
C R Boustred
(CR)
H Brittain
(H)
M A Brown
(MA)
Marc J Caulfield
(MJ)
G C Chan
(GC)
T Fowler
(T)
A Giess
(A)
A Hamblin
(A)
S Henderson
(S)
T J P Hubbard
(TJP)
R Jackson
(R)
L J Jones
(LJ)
D Kasperaviciute
(D)
M Kayikci
(M)
A Kousathanas
(A)
L Lahnstein
(L)
S E A Leigh
(SEA)
I U S Leong
(IUS)
F J Lopez
(FJ)
F Maleady-Crowe
(F)
M McEntagart
(M)
F Minneci
(F)
L Moutsianas
(L)
M Mueller
(M)
N Murugaesu
(N)
A C Need
(AC)
P O'Donovan
(P)
C A Odhams
(CA)
C Patch
(C)
D Perez-Gil
(D)
M B Pereira
(MB)
J Pullinger
(J)
T Rahim
(T)
A Rendon
(A)
T Rogers
(T)
K Savage
(K)
K Sawant
(K)
R H Scott
(RH)
A Siddiq
(A)
A Sieghart
(A)
S C Smith
(SC)
Alona Sosinsky
(A)
A Stuckey
(A)
M Tanguy
(M)
A L Taylor Tavares
(AL)
E R A Thomas
(ERA)
S R Thompson
(SR)
A Tucci
(A)
M J Welland
(MJ)
E Williams
(E)
K Witkowska
(K)
S M Wood
(SM)
James Allan
(J)
Garry Bisshopp
(G)
Stuart Blakemore
(S)
Jacqueline Boultwood
(J)
David Bruce
(D)
Francesca Buffa
(F)
Andrea Buggins
(A)
Gerald Cohen
(G)
Kate Cwynarski
(K)
Claire Dearden
(C)
Richard Dillon
(R)
Sarah Ennis
(S)
Francesco Falciani
(F)
George Follows
(G)
Francesco Forconi
(F)
Jade Forster
(J)
Christopher Fox
(C)
John Gribben
(J)
Anna Hockaday
(A)
Dena Howard
(D)
Andrew Jackson
(A)
Nagesh Kalakonda
(N)
Umair Khan
(U)
Philip Law
(P)
Pascal Lefevre
(P)
Ke Lin
(K)
Sandra Maseno
(S)
Paul Moss
(P)
Graham Packham
(G)
Claire Palles
(C)
Helen Parker
(H)
Piers Patten
(P)
Andrea Pellagatti
(A)
Guy Pratt
(G)
Alan Ramsay
(A)
Andy Rawstron
(A)
Matthew Rose-Zerilli
(M)
Joseph Slupsky
(J)
Tatjana Stankovic
(T)
Andrew Steele
(A)
Jonathan Strefford
(J)
Shankar Varadarajan
(S)
Dimitrios V Vavoulis
(DV)
Simon Wagner
(S)
David Westhead
(D)
Sarah Wordsworth
(S)
Jack Zhuang
(J)
Informations de copyright
© 2022. The Author(s).
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