The Discovery of a New Mutation Offers Insight
While rare, Wilms tumor is the most common pediatric kidney tumor and the fourth-most common childhood cancer, affecting one in every 10,000 children. While treatable, the cause in most cases remains unknown. Scientists at Northwestern Medicine, led by Elizabeth Perlman, MD, recently discovered a genetic mutation that could offer new insight.
The study describes a specific mutation found in the MLLT1 gene. MLLT1 is a critical component of gene transcription, the first step in gene expression, during early development. Dr. Perlman, a professor of Pathology at Northwestern University Feinberg School of Medicine, had previously led research that revealed a connection between Wilms tumors and mutations in the SIX1/2, DGCR8 and DROSHA genes. Three of the four genes – MLLT1, DGCR8 and DROSHA – are part of the basic cellular machinery that controls gene expression.
When Northwestern Medicine scientists sequenced DNA from tumor samples, they discovered that Wilms tumors could be caused by the new MLLT1 mutation, which results in tumors at a younger age and with different features than the previously known mutations. Their analysis showed that the MLLT1 mutation changed gene expression and protein binding, suggesting that MLLT1 abnormalities early in kidney development could lead to Wilms tumors.
The study puts forth that the origin of Wilms tumor is specific to gene mutations that occur only in the developing kidney. Identifying these mutations may represent new targets for therapies that can help young patients.
Interested in hearing more from Northwestern Medicine? Sign up for the Healthy Tips E‑Newsletter for everything from health and wellness ideas to patient breakthroughs to academic and medical advancements.