Title: The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Authors: Zhang, Jinghui ×
Ding, Li
Holmfeldt, Linda
Wu, Gang
Heatley, Sue L
Payne-Turner, Debbie
Easton, John
Chen, Xiang
Wang, Jianmin
Rusch, Michael
Chen, Shann-Ching
Wei, Lei
Collins-Underwood, J Racquel
Roberts, Kathryn G
Pounds, Stanley B
Ulyanov, Anatoly
Becksfort, Jared
Gupta, Pankaj
Huether, Robert
Kriwacki, Richard W
Parker, Matthew
McGoldrick, Daniel J
Zhao, David
Alford, Daniel
Espy, Stephen
Bobba, Kiran Chand
Song, Guangchun
Pei, Deqing
Cheng, Cheng
Roberts, Stefan
Barbato, Michael I
Campana, Dario
Coustan-Smith, Elaine
Shurtleff, Sheila A
Raimondi, Susana C
Kleppe, Maria
Cools, Jan
Shimano, Kristin A
Hermiston, Michelle L
Doulatov, Sergei
Eppert, Kolja
Laurenti, Elisa
Notta, Faiyaz
Dick, John E
Basso, Giuseppe
Hunger, Stephen P
Loh, Mignon L
Devidas, Meenakshi
Wood, Brent
Winter, Stuart
Dunsmore, Kimberley P
Fulton, Robert S
Fulton, Lucinda L
Hong, Xin
Harris, Christopher C
Dooling, David J
Ochoa, Kerri
Johnson, Kimberly J
Obenauer, John C
Evans, William E
Pui, Ching-Hon
Naeve, Clayton W
Ley, Timothy J
Mardis, Elaine R
Wilson, Richard K
Downing, James R
Mullighan, Charles G #
Issue Date: Jan-2012
Publisher: Nature Publishing Group
Series Title: Nature vol:481 issue:7380 pages:157-163
Article number: 10.1038/nature10725
Abstract: Early 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.
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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