Document Type
Journal Article
Publication Date
1-1-2015
Journal
Nature Communications
Volume
6
DOI
10.1038/ncomms10013
Keywords
Kidney Neoplasms--genetics; Neoplasm Proteins--genetics; Nuclear Proteins--genetics; Transcription Factors--genetics; Wilms Tumor--genetics
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Perlman, E., Gadd, S., Arold, S., Radhakrishnan, A., Gerhard, D., Dome, J. S., & +19 additional authors (2015). MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours.. Nature Communications, 6 (). http://dx.doi.org/10.1038/ncomms10013
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Nature Communications.