To evaluate expression domains and the pathogenic significance of SIX2 and CITED1 across WT, the Children's Oncology Group provided 40 WT specimens of stages I to IV (n = 10 per stage), which were enriched for unfavorable histology (n = 20) and treatment failure (relapse or death, n = 20).
Accordingly, methylation-specific quantitative polymerase chain reaction demonstrated promoter hypomethylation of WT1, PAX2, and SIX2 in primary WT and fetal kidneys, whereas progressive WT xenografts showed hypermethylation of SIX2, possibly leading to loss of renal differentiation.