Identification of Molecular Biomarkers in Taiwanese Patients with Wilms Tumor Using a Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA)-Based Approach

Abstract

Background: Wilms tumor is a solid tumor that frequently occurs in children. Genetic or epigenetic aberrations in WT1 and WT2 loci are implicated in its etiology. Moreover, tumor suppressor genes are frequently silenced by methylation in this tumor. Methods: In the present study, we analyzed the methylation statuses of promoter regions of 24 different tumor suppressor genes using a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)-based approach in six Wilms tumors. Results: All six Wilms tumors showed methylation of RASSF1 specific to tumors, not in normal tissues. Moreover, methylated HIC1 was identified in stromal type Wilms tumors and methylated BRCA1 was identified in epithelial type Wilms tumors. Unmethylated CASP8, RARB, MLH1_167, APC, and CDKN2A were found only in blastemal predominant type Wilms tumors. Conclusions: Our results indicated that methylation of RASSF1 is the essential event in the tumorigenesis of Wilms tumor, which may inform its clinical and therapeutic management. In addition, mixed type Wilms tumors may be classified according to epithelial, stromal, and blastemal components via MS-MLPA-based approach.