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MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

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 do...

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Autores principales: Perlman, Elizabeth J., Gadd, Samantha, Arold, Stefan T., Radhakrishnan, Anand, Gerhard, Daniela S., Jennings, Lawrence, Huff, Vicki, Guidry Auvil, Jaime M., 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686660/
https://www.ncbi.nlm.nih.gov/pubmed/26635203
http://dx.doi.org/10.1038/ncomms10013
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author Perlman, Elizabeth J.
Gadd, Samantha
Arold, Stefan T.
Radhakrishnan, Anand
Gerhard, Daniela S.
Jennings, Lawrence
Huff, Vicki
Guidry Auvil, Jaime M.
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.
author_facet Perlman, Elizabeth J.
Gadd, Samantha
Arold, Stefan T.
Radhakrishnan, Anand
Gerhard, Daniela S.
Jennings, Lawrence
Huff, Vicki
Guidry Auvil, Jaime M.
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.
author_sort Perlman, Elizabeth J.
collection PubMed
description 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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spelling pubmed-46866602016-01-07 MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours Perlman, Elizabeth J. Gadd, Samantha Arold, Stefan T. Radhakrishnan, Anand Gerhard, Daniela S. Jennings, Lawrence Huff, Vicki Guidry Auvil, Jaime M. 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. Nat Commun Article 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. Nature Publishing Group 2015-12-04 /pmc/articles/PMC4686660/ /pubmed/26635203 http://dx.doi.org/10.1038/ncomms10013 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Perlman, Elizabeth J.
Gadd, Samantha
Arold, Stefan T.
Radhakrishnan, Anand
Gerhard, Daniela S.
Jennings, Lawrence
Huff, Vicki
Guidry Auvil, Jaime M.
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
title MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
title_full MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
title_fullStr MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
title_full_unstemmed MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
title_short MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours
title_sort mllt1 yeats domain mutations in clinically distinctive favourable histology wilms tumours
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686660/
https://www.ncbi.nlm.nih.gov/pubmed/26635203
http://dx.doi.org/10.1038/ncomms10013
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