Interactions with transcriptional co-factors and/or cooperation with wild-type SIX1/2 or with other common Wilms tumor-associated mutations – such as the DGCR8/DROSHA mutations mentioned earlier, or loss of imprinting/loss of heterozygosity at chromosome 11p15 resulting in the overexpression of IGF2 (affecting an estimated 75–80% of FHWT and blastemal tumors) (Walz et al., 2015; Wegert et al., 2015) – might be necessary to enhance the regulatory effect of SIX1/2-Q177R and will require further investigation. The gene discussed is SIX1; the disease is Nephroblastoma.