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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
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Journal Article
Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
2014
Overview
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.
Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.
Publisher
Nature Publishing Group UK,Nature Publishing Group
