The genomic landscape of pediatric acute lymphoblastic leukemia.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
16
07
2021
accepted:
13
07
2022
pubmed:
2
9
2022
medline:
16
9
2022
entrez:
1
9
2022
Statut:
ppublish
Résumé
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.
Identifiants
pubmed: 36050548
doi: 10.1038/s41588-022-01159-z
pii: 10.1038/s41588-022-01159-z
pmc: PMC9700506
mid: NIHMS1848401
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1376-1389Subventions
Organisme : NCI NIH HHS
ID : R35 CA197695
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216391
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA241297
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115279
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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