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MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

Nat Commun. Volume 6: 10013, 4 December 2016, 10.1038/ncomms10013

Wilms tumor is an embryonal tumor of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumors remain largely unknown. Here we identify recurrent mutations within Wilms tumors 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 tumors show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumors 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 tumor.

This study characterized TARGET cases as described below:

Study cohort (75 cases)
75 cases had chip-based GE
75 cases had mRNA-Seq
75 cases had miRNA-Seq
75 cases had CN array
75 cases had methylation array
56 cases had WGS
23 cases had WXS
75 cases had TCS

GE=gene expression; CN=copy number, TCS=targeted capture sequencing

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