Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia

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Item Type:	Article
Title:	Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
Creators Name:	Mar, B.G., Bullinger, L.B., McLean, K.M., Grauman, P.V., Harris, M.H., Stevenson, K., Neuberg, D.S., Sinha, A.U., Sallan, S.E., Silverman, L.B., Kung, A.L., Lo Nigro, L., Ebert, B.L. and Armstrong, S.A.
Abstract:	Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here, we sequence genes encoding epigenetic regulators in matched diagnosis–remission–relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signalling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance.
Keywords:	Base Sequence, DNA Primers, DNA Sequence Analysis, Exons, Genetic Epigenesis, Histone-Lysine N-Methyltransferase, Molecular Sequence Data, Mutation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence, Treatment Failure
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	5
Page Range:	3469
Date:	24 March 2014
Official Publication:	https://doi.org/10.1038/ncomms4469
PubMed:	View item in PubMed

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