The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms

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Description

<jats:title>Abstract</jats:title><jats:p>Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. 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 84 pediatric tMN cases (tMDS: <jats:italic>n</jats:italic> = 28, tAML: <jats:italic>n</jats:italic> = 56). Our data show that Ras/MAPK pathway mutations, alterations in <jats:italic>RUNX1</jats:italic> or <jats:italic>TP53</jats:italic>, and <jats:italic>KMT2A</jats:italic> rearrangements are frequent somatic drivers, and we identify cases with aberrant <jats:italic>MECOM</jats:italic> expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with <jats:italic>TP53</jats:italic> mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.</jats:p>

Journal

  • Nature Communications

    Nature Communications 12 (1), 985-, 2021-02-12

    Springer Science and Business Media LLC

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