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MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms10013

2041-1723

Elizabeth J. Perlman, Samantha 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 C. Anderson, Yussanne Ma, Andrew J. Mungall, Richard A. Moore, Marco A. Marra, Charles G. Mullighan, Jing Ma, David A. Wheeler, Oliver Hampton, Julie M. Gastier‐Foster, Nicole Ross, Malcolm A. Smith,

Renal cell carcinoma treatment

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.