MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

Elizabeth J Perlman; Samantha Gadd; Stefan T. Arold; Anand Radhakrishnan; Daniela S. Gerhard; Lawrence Jennings; Vicki Huff; Jaime M. Guidry Auvil; Tanja M. Davidsen; Jeffrey S. Dome; Daoud Meerzaman; Chih Hao Hsu; Cu Nguyen; James Anderson; Yussanne Ma; Andrew J Mungall; Richard A. Moore; Marco A. Marra; Charles G Mullighan; Jing Ma; David A. Wheeler; Oliver A. Hampton; Julie M. Gastier-Foster; Nicole Ross; Malcolm A Smith

doi:10.1038/ncomms10013

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

Elizabeth J Perlman, Samantha Gadd, Stefan T. Arold, Anand Radhakrishnan, Daniela S. Gerhard, Lawrence Jennings, Vicki Huff, Jaime M. Guidry Auvil, Tanja M. Davidsen, Jeffrey S. Dome, Daoud Meerzaman, Chih Hao Hsu, Cu Nguyen, James Anderson, Yussanne Ma, Andrew J Mungall, Richard A. Moore, Marco A. Marra, Charles G Mullighan, Jing MaDavid A. Wheeler, Oliver A. Hampton, Julie M. Gastier-Foster, Nicole Ross, Malcolm A Smith

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Abstract

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

Original language	English (US)
Journal	Nature Communications
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/ncomms10013
State	Published - Dec 4 2015

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Perlman, E. J., Gadd, S., Arold, S. T., Radhakrishnan, A., Gerhard, D. S., Jennings, L., Huff, V., Guidry Auvil, J. M., Davidsen, T. M., Dome, J. S., Meerzaman, D., Hsu, C. H., Nguyen, C., Anderson, J., Ma, Y., Mungall, A. J., Moore, R. A., Marra, M. A., Mullighan, C. G., ... Smith, M. A. (2015). MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours. Nature Communications, 6(1). https://doi.org/10.1038/ncomms10013

@article{f3ec7a48875049d2aa50646563769376,

title = "MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours",

abstract = "Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.",

author = "Perlman, {Elizabeth J} and Samantha Gadd and Arold, {Stefan T.} and Anand Radhakrishnan and Gerhard, {Daniela S.} and Lawrence Jennings and Vicki Huff and {Guidry Auvil}, {Jaime M.} and Davidsen, {Tanja M.} and Dome, {Jeffrey S.} and Daoud Meerzaman and Hsu, {Chih Hao} and Cu Nguyen and James Anderson and Yussanne Ma and Mungall, {Andrew J} and Moore, {Richard A.} and Marra, {Marco A.} and Mullighan, {Charles G} and Jing Ma and Wheeler, {David A.} and Hampton, {Oliver A.} and Gastier-Foster, {Julie M.} and Nicole Ross and Smith, {Malcolm A}",

note = "KAUST Repository Item: Exported on 2020-10-01",

year = "2015",

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day = "4",

doi = "10.1038/ncomms10013",

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Perlman, EJ, Gadd, S, Arold, ST, Radhakrishnan, A, Gerhard, DS, Jennings, L, Huff, V, Guidry Auvil, JM, Davidsen, TM, Dome, JS, Meerzaman, D, Hsu, CH, Nguyen, C, Anderson, J, Ma, Y, Mungall, AJ, Moore, RA, Marra, MA, Mullighan, CG, Ma, J, Wheeler, DA, Hampton, OA, Gastier-Foster, JM, Ross, N & Smith, MA 2015, 'MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours', Nature Communications, vol. 6, no. 1. https://doi.org/10.1038/ncomms10013

TY - JOUR

T1 - MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

AU - Perlman, Elizabeth J

AU - Gadd, Samantha

AU - Arold, Stefan T.

AU - Radhakrishnan, Anand

AU - Gerhard, Daniela S.

AU - Jennings, Lawrence

AU - Huff, Vicki

AU - Guidry Auvil, Jaime M.

AU - Davidsen, Tanja M.

AU - Dome, Jeffrey S.

AU - Meerzaman, Daoud

AU - Hsu, Chih Hao

AU - Nguyen, Cu

AU - Anderson, James

AU - Ma, Yussanne

AU - Mungall, Andrew J

AU - Moore, Richard A.

AU - Marra, Marco A.

AU - Mullighan, Charles G

AU - Ma, Jing

AU - Wheeler, David A.

AU - Hampton, Oliver A.

AU - Gastier-Foster, Julie M.

AU - Ross, Nicole

AU - Smith, Malcolm A

N1 - KAUST Repository Item: Exported on 2020-10-01

PY - 2015/12/4

Y1 - 2015/12/4

N2 - Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

AB - Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

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DO - 10.1038/ncomms10013

M3 - Article

C2 - 26635203

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

Abstract

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