Abstract
A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms’ tumor, clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), rhabdoid tumor of the kidney (RTK), and the Ewing’s sarcoma family of tumors (ESFT). By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK), and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms’ tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors.
Highlights
In the pediatric population, the types of renal tumor are entirely different from those occurring in adults
It is estimated that 85% of pediatric renal malignancies comprise nephroblastoma, 5% congenital mesoblastic nephroma (CMN), 4% clear cell sarcoma of the kidney (CCSK), and 2% rhabdoid tumor of the kidney (RTK) [1], and these 4 major entities account for 96% of the total
We carried out a DNA methylation analysis to identify genes differentially methylated in a series of pediatric tumors and we clearly showed that different pediatric sarcomas occurring in the kidney possess a distinct DNA methylation profile
Summary
The types of renal tumor are entirely different from those occurring in adults. It is estimated that 85% of pediatric renal malignancies comprise nephroblastoma, 5% congenital mesoblastic nephroma (CMN), 4% clear cell sarcoma of the kidney (CCSK), and 2% rhabdoid tumor of the kidney (RTK) [1], and these 4 major entities account for 96% of the total. Nephroblastoma is malignant but still a relatively favorable tumor prognostically, being derived from nephrogenic blastemal cells that can show divergent differentiation. CCSK is a relatively unfavorable tumor prognostically, being composed of clear mesenchymal cells with a characteristic vascular pattern [3]. RTK is a highly aggressive tumor occurring in young children, has a dismal outcome, and is characterized by pathological rhabdoid features and molecular biallelic inactivation of the SMARCB1 (hSNF5/INI1) gene [4,5,6]
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