The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

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dc.contributor.authorZhang, J.
dc.contributor.authorDing, L.
dc.contributor.authorHolmfeldt, L.
dc.contributor.authorWu, G.
dc.contributor.authorHeatley, S.
dc.contributor.authorPayne-Turner, D.
dc.contributor.authorEaston, J.
dc.contributor.authorChen, X.
dc.contributor.authorWang, J.
dc.contributor.authorRusch, M.
dc.contributor.authorLu, C.
dc.contributor.authorChen, S.-C.
dc.contributor.authorWei, L.
dc.contributor.authorCollins-Underwood, J.
dc.contributor.authorMa, J.
dc.contributor.authorRoberts, K.
dc.contributor.authorPounds, S.
dc.contributor.authorUlyanov, A.
dc.contributor.authorBecksfort, J.
dc.contributor.authorGupta, P.
dc.contributor.authoret al.
dc.date.issued2012
dc.description.abstractEarly T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
dc.description.statementofresponsibilityJinghui Zhang, Li Ding, Linda Holmfeldt, Gang Wu, Sue L. Heatley, Debbie Payne-Turner, John Easton, Xiang Chen, Jianmin Wang, Michael Rusch, Charles Lu, Shann-Ching Chen, Lei Wei, J. Racquel Collins-Underwood, Jing Ma, Kathryn G. Roberts, Stanley B. Pounds, Anatoly Ulyanov, Jared Becksfort, Pankaj Gupta, Robert Huether, Richard W. Kriwacki, Matthew Parker, Daniel J. McGoldrick, David Zhao, Daniel Alford, Stephen Espy, Kiran Chand Bobba, Guangchun Song, Deqing Pei, Cheng Cheng, Stefan Roberts, Michael I. Barbato, Dario Campana, Elaine Coustan-Smith, Sheila A. Shurtleff, Susana C. Raimondi, Maria Kleppe, Jan Cools, Kristin A. Shimano, Michelle L. Hermiston, Sergei Doulatov, Kolja Eppert, Elisa Laurenti, Faiyaz Notta, John E. Dick, Giuseppe Basso, Stephen P. Hunger, Mignon L. Loh, Meenakshi Devidas, Brent Wood, Stuart Winter, Kimberley P. Dunsmore, Robert S. Fulton, Lucinda L. Fulton, Xin Hong, Christopher C. Harris, David J. Dooling, Kerri Ochoa, Kimberly J. Johnson, John C. Obenauer, William E. Evans, Ching-Hon Pui, Clayton W. Naeve, Timothy J. Ley, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Charles G. Mullighan
dc.identifier.citationNature, 2012; 481(7380):157-163
dc.identifier.doi10.1038/nature10725
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidHeatley, S. [0000-0001-7497-6477]
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/104426
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights©2012 Macmillan Publishers Limited. All rights reserved.
dc.source.urihttps://doi.org/10.1038/nature10725
dc.subjectCancer; Genetics; Genomics; Health and medicine; Molecular biology
dc.titleThe genetic basis of early T-cell precursor acute lymphoblastic leukaemia
dc.typeJournal article
pubs.publication-statusPublished

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