DNA methylation biomarkers predict Wilms tumor disease progression

Wilms tumor (WT), also known as nephroblastoma, is the most commonly observed renal tumor within the genitourinary tract of children and constitutes 5% of all childhood malignancies. In this study, we used microarray technology to explore methylation patterns in both WT and adjacent healthy tissues from excised kidneys prior to any chemotherapy treatment in stage I and II WTs. We report several differentially methylated regions that show potential as prognostic biomarkers for disease relapse, and overall patient survival. To explain the mechanistic role of DNA methylation changes in WT relapse, we explore the genes controlled by the differentially methylated IGF2 region, and show elevated expression of INS-IGF2 transcript in tumour tissue of patients that have relapsed after treatment. Altogether, this study provides insights into causes of chemotherapy resistance in patients with low risk WT. In the aim to identify methylation biomarkers for disease prognosis, tumor and normal FFPE tissue samples that were surgically removed before treatment were collected from the Pathology department from nine patients who had complete response to treatment and nine patients who had recurrent disease. DNA samples were analyzed Illumina Infinium Human Methylation EPIC bead chips.