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


Authors: Schwartz, J. R.; Ma, J.; Kamens, J.; Westover, T.; Walsh, M. P.; Brady, S. W.; Michael, J. R.; Chen, X.; Montefiori, L.; Song, G.; Wu, G.; Wu, H.; Branstetter, C.; Hiltenbrand, R.; Walsh, M. F.; Nichols, K. E.; Maciaszek, J. L.; Liu, Y.; Kumar, P.; Easton, J.; Newman, S.; Rubnitz, J. E.; Mullighan, C. G.; Pounds, S.; Zhang, J.; Gruber, T.; Ma, X.; Klco, J. M.
Article Title: The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms
Abstract: 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: n = 28, 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 tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 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. © 2021, The Author(s).
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-02-12
Start Page: 985
Language: English
DOI: 10.1038/s41467-021-21255-8
PROVIDER: scopus
PMCID: PMC7880998
PUBMED: 33579957
DOI/URL:
Notes: Article -- Export Date: 1 March 2021 -- Source: Scopus
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  1. Michael Francis Walsh
    156 Walsh