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The Acquisition of Molecular Drivers in Pediatric Therapy-Related Myeloid Neoplasms

Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis1-4. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 85 pediatric tMN cases (tMDS: n=29, tAML: n=56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN5-7, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases were unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006674 Illumina HiSeq 2000 56
EGAD00001006675 Illumina HiSeq 2000 137
EGAD00001006676 Illumina HiSeq 2000 35
Publications Citations
The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms.
Nat Commun 12: 2021 985
25
Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.
Nat Commun 14: 2023 1739
3