Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

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Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. / Xu, Heng; Zhang, Hui; Yang, Wenjian; Yadav, Rachita; Morrison, Alanna C; Qian, Maoxiang; Devidas, Meenakshi; Liu, Yu; Perez-Andreu, Virginia; Zhao, Xujie; Gastier-Foster, Julie M; Lupo, Philip J; Neale, Geoff; Raetz, Elizabeth; Larsen, Eric; Bowman, W Paul; Carroll, William L; Winick, Naomi; Williams, Richard; Hansen, Torben; Holm, Jens-Christian; Mardis, Elaine; Fulton, Robert; Pui, Ching-Hon; Zhang, Jinghui; Mullighan, Charles G; Evans, William E; Hunger, Stephen P; Gupta, Ramneek; Schmiegelow, K.; Loh, Mignon L; Relling, Mary V; Yang, Jun J.

In: Nature Communications, Vol. 6, 7553, 2015, p. 1-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Xu, H, Zhang, H, Yang, W, Yadav, R, Morrison, AC, Qian, M, Devidas, M, Liu, Y, Perez-Andreu, V, Zhao, X, Gastier-Foster, JM, Lupo, PJ, Neale, G, Raetz, E, Larsen, E, Bowman, WP, Carroll, WL, Winick, N, Williams, R, Hansen, T, Holm, J-C, Mardis, E, Fulton, R, Pui, C-H, Zhang, J, Mullighan, CG, Evans, WE, Hunger, SP, Gupta, R, Schmiegelow, K, Loh, ML, Relling, MV & Yang, JJ 2015, 'Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children', Nature Communications, vol. 6, 7553, pp. 1-7. https://doi.org/10.1038/ncomms8553

APA

Xu, H., Zhang, H., Yang, W., Yadav, R., Morrison, A. C., Qian, M., Devidas, M., Liu, Y., Perez-Andreu, V., Zhao, X., Gastier-Foster, J. M., Lupo, P. J., Neale, G., Raetz, E., Larsen, E., Bowman, W. P., Carroll, W. L., Winick, N., Williams, R., ... Yang, J. J. (2015). Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. Nature Communications, 6, 1-7. [7553]. https://doi.org/10.1038/ncomms8553

Vancouver

Xu H, Zhang H, Yang W, Yadav R, Morrison AC, Qian M et al. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. Nature Communications. 2015;6:1-7. 7553. https://doi.org/10.1038/ncomms8553

Author

Xu, Heng ; Zhang, Hui ; Yang, Wenjian ; Yadav, Rachita ; Morrison, Alanna C ; Qian, Maoxiang ; Devidas, Meenakshi ; Liu, Yu ; Perez-Andreu, Virginia ; Zhao, Xujie ; Gastier-Foster, Julie M ; Lupo, Philip J ; Neale, Geoff ; Raetz, Elizabeth ; Larsen, Eric ; Bowman, W Paul ; Carroll, William L ; Winick, Naomi ; Williams, Richard ; Hansen, Torben ; Holm, Jens-Christian ; Mardis, Elaine ; Fulton, Robert ; Pui, Ching-Hon ; Zhang, Jinghui ; Mullighan, Charles G ; Evans, William E ; Hunger, Stephen P ; Gupta, Ramneek ; Schmiegelow, K. ; Loh, Mignon L ; Relling, Mary V ; Yang, Jun J. / Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. In: Nature Communications. 2015 ; Vol. 6. pp. 1-7.

Bibtex

@article{2ce4501c35874abf9e9535cae05b21d3,
title = "Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children",
abstract = "There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10−23, odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16INK4A, increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A–CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A–CDKN2B tumour suppressors in leukaemogenesis.",
author = "Heng Xu and Hui Zhang and Wenjian Yang and Rachita Yadav and Morrison, {Alanna C} and Maoxiang Qian and Meenakshi Devidas and Yu Liu and Virginia Perez-Andreu and Xujie Zhao and Gastier-Foster, {Julie M} and Lupo, {Philip J} and Geoff Neale and Elizabeth Raetz and Eric Larsen and Bowman, {W Paul} and Carroll, {William L} and Naomi Winick and Richard Williams and Torben Hansen and Jens-Christian Holm and Elaine Mardis and Robert Fulton and Ching-Hon Pui and Jinghui Zhang and Mullighan, {Charles G} and Evans, {William E} and Hunger, {Stephen P} and Ramneek Gupta and K. Schmiegelow and Loh, {Mignon L} and Relling, {Mary V} and Yang, {Jun J}",
year = "2015",
doi = "10.1038/ncomms8553",
language = "English",
volume = "6",
pages = "1--7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

AU - Xu, Heng

AU - Zhang, Hui

AU - Yang, Wenjian

AU - Yadav, Rachita

AU - Morrison, Alanna C

AU - Qian, Maoxiang

AU - Devidas, Meenakshi

AU - Liu, Yu

AU - Perez-Andreu, Virginia

AU - Zhao, Xujie

AU - Gastier-Foster, Julie M

AU - Lupo, Philip J

AU - Neale, Geoff

AU - Raetz, Elizabeth

AU - Larsen, Eric

AU - Bowman, W Paul

AU - Carroll, William L

AU - Winick, Naomi

AU - Williams, Richard

AU - Hansen, Torben

AU - Holm, Jens-Christian

AU - Mardis, Elaine

AU - Fulton, Robert

AU - Pui, Ching-Hon

AU - Zhang, Jinghui

AU - Mullighan, Charles G

AU - Evans, William E

AU - Hunger, Stephen P

AU - Gupta, Ramneek

AU - Schmiegelow, K.

AU - Loh, Mignon L

AU - Relling, Mary V

AU - Yang, Jun J

PY - 2015

Y1 - 2015

N2 - There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10−23, odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16INK4A, increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A–CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A–CDKN2B tumour suppressors in leukaemogenesis.

AB - There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10−23, odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16INK4A, increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A–CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A–CDKN2B tumour suppressors in leukaemogenesis.

U2 - 10.1038/ncomms8553

DO - 10.1038/ncomms8553

M3 - Journal article

C2 - 26104880

VL - 6

SP - 1

EP - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7553

ER -

ID: 150710223