DNA methylation biomarkers predict Wilms tumor disease progression. 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. Overall design: 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.

肾母细胞瘤（Wilms tumor, WT），亦称肾胚胎瘤（nephroblastoma），是儿童泌尿生殖道最常见的肾脏肿瘤，占所有儿童恶性肿瘤的5%。本研究采用微阵列技术，针对Ⅰ期与Ⅱ期肾母细胞瘤患者，分析其化疗前切除的肿瘤组织及配对毗邻正常肾脏组织的甲基化特征。本研究鉴定出多个差异甲基化区域，其有望作为疾病复发及患者总生存期的预后生物标志物。为阐明DNA甲基化改变在肾母细胞瘤复发中的机制作用，本研究对差异甲基化IGF2区域调控的基因进行了探究，并证实复发患者肿瘤组织中INS-IGF2转录本的表达水平显著升高。综上，本研究为低风险肾母细胞瘤患者的化疗耐药成因提供了新的见解。

实验设计：为筛选疾病预后相关的甲基化生物标志物，本研究从病理科收集了18例患者的治疗前手术切除样本，其中9例为治疗完全应答者，9例为复发患者，样本涵盖肿瘤组织与配对正常福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）组织。本研究采用Illumina Infinium Human Methylation EPIC bead chips对DNA样本进行检测分析。