MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

Elizabeth J Perlman*, Samantha L Gadd, Stefan T. Arold, Anand Radhakrishnan, Daniela S. Gerhard, Lawrence J 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

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 languageEnglish (US)
Article number10013
JournalNature communications
Volume6
DOIs
StatePublished - Dec 4 2015

Fingerprint

Histology
histology
Wilms Tumor
mutations
Tumors
tumors
Mutation
Kidney
Neoplasms
Mutant Proteins
Histones
Gene Expression
gene expression
kidneys
Gene expression
genes
elongation
Elongation
Genes
proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Perlman, Elizabeth J ; Gadd, Samantha L ; Arold, Stefan T. ; Radhakrishnan, Anand ; Gerhard, Daniela S. ; Jennings, Lawrence J ; Huff, Vicki ; Auvil, Jaime M.Guidry ; Davidsen, Tanja M. ; Dome, Jeffrey S. ; Meerzaman, Daoud ; Hsu, Chih Hao ; Nguyen, Cu ; Anderson, James ; Ma, Yussanne ; Mungall, Andrew J. ; Moore, Richard A. ; Marra, Marco A. ; Mullighan, Charles G. ; Ma, Jing ; Wheeler, David A. ; Hampton, Oliver A. ; Gastier-Foster, Julie M. ; Ross, Nicole ; Smith, Malcolm A. / MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours. In: Nature communications. 2015 ; Vol. 6.
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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.",
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Perlman, EJ, Gadd, SL, Arold, ST, Radhakrishnan, A, Gerhard, DS, Jennings, LJ, Huff, V, Auvil, JMG, 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, 10013. https://doi.org/10.1038/ncomms10013

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours. / Perlman, Elizabeth J; Gadd, Samantha L; Arold, Stefan T.; Radhakrishnan, Anand; Gerhard, Daniela S.; Jennings, Lawrence J; Huff, Vicki; Auvil, Jaime M.Guidry; Davidsen, Tanja M.; Dome, Jeffrey S.; Meerzaman, Daoud; Hsu, Chih Hao; Nguyen, Cu; Anderson, James; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Gastier-Foster, Julie M.; Ross, Nicole; Smith, Malcolm A.

In: Nature communications, Vol. 6, 10013, 04.12.2015.

Research output: Contribution to journalArticle

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

AU - Perlman, Elizabeth J

AU - Gadd, Samantha L

AU - Arold, Stefan T.

AU - Radhakrishnan, Anand

AU - Gerhard, Daniela S.

AU - Jennings, Lawrence J

AU - Huff, Vicki

AU - Auvil, Jaime M.Guidry

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.

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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