| Literature DB >> 33579957 |
Jason R Schwartz1, Jing Ma2, Jennifer Kamens3, Tamara Westover2, Michael P Walsh2, Samuel W Brady4, J Robert Michael4, Xiaolong Chen4, Lindsey Montefiori2, Guangchun Song2, Gang Wu4, Huiyun Wu5, Cristyn Branstetter6, Ryan Hiltenbrand2, Michael F Walsh7, Kim E Nichols8, Jamie L Maciaszek8, Yanling Liu4, Priyadarshini Kumar2, John Easton4, Scott Newman4, Jeffrey E Rubnitz8, Charles G Mullighan2, Stanley Pounds5, Jinghui Zhang4, Tanja Gruber9,10, Xiaotu Ma11, Jeffery M Klco12.
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.Entities:
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Year: 2021 PMID： 33579957 PMCID： PMC7880998 DOI： 10.1038/s41467-021-21255-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919