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.
Authors in the journal Nature Communications 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.