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

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The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. / Andersson, Anna; Ma, Jing; Wang, Jianmin; Chen, Xiang; Gedman, Amanda Larson; Dang, Jinjun; Nakitandwe, Joy; Holmfeldt, Linda; Parker, Matthew; Easton, John; Huether, Robert; Kriwacki, Richard; Rusch, Michael; Wu, Gang; Li, Yongjin; Mulder, Heather; Raimondi, Susana; Pounds, Stanley; Kang, Guolian; Shi, Lei; Becksfort, Jared; Gupta, Pankaj; Payne-Turner, Debbie; Vadodaria, Bhavin; Boggs, Kristy; Yergeau, Donald; Manne, Jayanthi; Song, Guangchun; Edmonson, Michael; Nagahawatte, Panduka; Wei, Lei; Cheng, Cheng; Pei, Deqing; Sutton, Rosemary; Venn, Nicola C; Chetcuti, Albert; Rush, Amanda; Catchpoole, Daniel; Heldrup, Jesper; Fioretos, Thoas; Lu, Charles; Ding, Li; Pui, Ching-Hon; Shurtleff, Sheila; Mullighan, Charles G; Mardis, Elaine R; Wilson, Richard K; Gruber, Tanja A; Zhang, Jinghui; Downing, James R.

I: Nature Genetics, Vol. 47, Nr. 4, 2015, s. 330-U192.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Andersson, A, Ma, J, Wang, J, Chen, X, Gedman, AL, Dang, J, Nakitandwe, J, Holmfeldt, L, Parker, M, Easton, J, Huether, R, Kriwacki, R, Rusch, M, Wu, G, Li, Y, Mulder, H, Raimondi, S, Pounds, S, Kang, G, Shi, L, Becksfort, J, Gupta, P, Payne-Turner, D, Vadodaria, B, Boggs, K, Yergeau, D, Manne, J, Song, G, Edmonson, M, Nagahawatte, P, Wei, L, Cheng, C, Pei, D, Sutton, R, Venn, NC, Chetcuti, A, Rush, A, Catchpoole, D, Heldrup, J, Fioretos, T, Lu, C, Ding, L, Pui, C-H, Shurtleff, S, Mullighan, CG, Mardis, ER, Wilson, RK, Gruber, TA, Zhang, J & Downing, JR 2015, 'The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.', Nature Genetics, vol. 47, nr. 4, s. 330-U192. https://doi.org/10.1038/ng.3230

APA

Andersson, A., Ma, J., Wang, J., Chen, X., Gedman, A. L., Dang, J., ... Downing, J. R. (2015). The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nature Genetics, 47(4), 330-U192. https://doi.org/10.1038/ng.3230

CBE

Andersson A, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder H, Raimondi S, Pounds S, Kang G, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagahawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, Lu C, Ding L, Pui C-H, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA, Zhang J, Downing JR. 2015. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nature Genetics. 47(4):330-U192. https://doi.org/10.1038/ng.3230

MLA

Vancouver

Author

Andersson, Anna ; Ma, Jing ; Wang, Jianmin ; Chen, Xiang ; Gedman, Amanda Larson ; Dang, Jinjun ; Nakitandwe, Joy ; Holmfeldt, Linda ; Parker, Matthew ; Easton, John ; Huether, Robert ; Kriwacki, Richard ; Rusch, Michael ; Wu, Gang ; Li, Yongjin ; Mulder, Heather ; Raimondi, Susana ; Pounds, Stanley ; Kang, Guolian ; Shi, Lei ; Becksfort, Jared ; Gupta, Pankaj ; Payne-Turner, Debbie ; Vadodaria, Bhavin ; Boggs, Kristy ; Yergeau, Donald ; Manne, Jayanthi ; Song, Guangchun ; Edmonson, Michael ; Nagahawatte, Panduka ; Wei, Lei ; Cheng, Cheng ; Pei, Deqing ; Sutton, Rosemary ; Venn, Nicola C ; Chetcuti, Albert ; Rush, Amanda ; Catchpoole, Daniel ; Heldrup, Jesper ; Fioretos, Thoas ; Lu, Charles ; Ding, Li ; Pui, Ching-Hon ; Shurtleff, Sheila ; Mullighan, Charles G ; Mardis, Elaine R ; Wilson, Richard K ; Gruber, Tanja A ; Zhang, Jinghui ; Downing, James R. / The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. I: Nature Genetics. 2015 ; Vol. 47, Nr. 4. s. 330-U192.

RIS

TY - JOUR

T1 - The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

AU - Andersson, Anna

AU - Ma, Jing

AU - Wang, Jianmin

AU - Chen, Xiang

AU - Gedman, Amanda Larson

AU - Dang, Jinjun

AU - Nakitandwe, Joy

AU - Holmfeldt, Linda

AU - Parker, Matthew

AU - Easton, John

AU - Huether, Robert

AU - Kriwacki, Richard

AU - Rusch, Michael

AU - Wu, Gang

AU - Li, Yongjin

AU - Mulder, Heather

AU - Raimondi, Susana

AU - Pounds, Stanley

AU - Kang, Guolian

AU - Shi, Lei

AU - Becksfort, Jared

AU - Gupta, Pankaj

AU - Payne-Turner, Debbie

AU - Vadodaria, Bhavin

AU - Boggs, Kristy

AU - Yergeau, Donald

AU - Manne, Jayanthi

AU - Song, Guangchun

AU - Edmonson, Michael

AU - Nagahawatte, Panduka

AU - Wei, Lei

AU - Cheng, Cheng

AU - Pei, Deqing

AU - Sutton, Rosemary

AU - Venn, Nicola C

AU - Chetcuti, Albert

AU - Rush, Amanda

AU - Catchpoole, Daniel

AU - Heldrup, Jesper

AU - Fioretos, Thoas

AU - Lu, Charles

AU - Ding, Li

AU - Pui, Ching-Hon

AU - Shurtleff, Sheila

AU - Mullighan, Charles G

AU - Mardis, Elaine R

AU - Wilson, Richard K

AU - Gruber, Tanja A

AU - Zhang, Jinghui

AU - Downing, James R

PY - 2015

Y1 - 2015

N2 - Infant 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.

AB - Infant 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.

U2 - 10.1038/ng.3230

DO - 10.1038/ng.3230

M3 - Article

VL - 47

SP - 330-U192

JO - Nature Genetics

T2 - Nature Genetics

JF - Nature Genetics

SN - 1546-1718

IS - 4

ER -