The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

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dc.contributor.authorAndersson, A.
dc.contributor.authorMa, J.
dc.contributor.authorWang, J.
dc.contributor.authorChen, X.
dc.contributor.authorGedman, A.
dc.contributor.authorDang, J.
dc.contributor.authorNakitandwe, J.
dc.contributor.authorHolmfeldt, L.
dc.contributor.authorParker, M.
dc.contributor.authorEaston, J.
dc.contributor.authorHuether, R.
dc.contributor.authorKriwacki, R.
dc.contributor.authorRusch, M.
dc.contributor.authorWu, G.
dc.contributor.authorLi, Y.
dc.contributor.authorMulder, H.
dc.contributor.authorRaimondi, S.
dc.contributor.authorPounds, S.
dc.contributor.authorKang, G.
dc.contributor.authorShi, L.
dc.contributor.authoret al.
dc.date.issued2015
dc.descriptionIncludes 3 unnumbered pages at the end of the article. Published online 2 March 2015
dc.description.abstractInfant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
dc.description.statementofresponsibilityAnna K Andersson ... Charles G Mullighan ... et al. for The St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
dc.identifier.citationNature Genetics, 2015; 47(4):330-337
dc.identifier.doi10.1038/ng.3230
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/106072
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2015 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/ng.3230
dc.subjectAcute lymphocytic leukaemia
dc.titleThe landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias
dc.typeJournal article
pubs.publication-statusPublished

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