The genomic landscape of pediatric B-lineage acute lymphoblastic leukemia

Mullighan Lab

Mullighan Lab

Mar 23, 2022

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Whole Genome Sequencing
Whole Exome Sequencing
SNP Array

In this view, the mutational landscape of B-ALL samples are stratified by subtype. Gene-centric views of the mutations can be viewed by clicking on the gene name along the vertical axis of the oncoprint. Sample information is available by mousing over each sample name on the horizontal axis of the oncoprint.

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.

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