title: DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.
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.
authors: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors: Hitomi
authors: H
authors: Ueno
authors: Hajime
authors: H
authors: Okita
authors: Shingo
authors: S
authors: Akimoto
authors: Kenichiro
authors: K
authors: Kobayashi
authors: Kazuhiko
authors: K
authors: Nakabayashi
authors: Kenichiro
authors: K
authors: Hata
authors: Junichiro
authors: J
authors: Fujimoto
authors: Jun-Ichi
authors: J
authors: Hata
authors: Masahiro
authors: M
authors: Fukuzawa
authors: Nobutaka
authors: N
authors: Kiyokawa
mesh_terms: D002648:Child; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003937:Diagnosis, Differential; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015183:Restriction Mapping; D018227:Sarcoma, Clear Cell / Q000175:diagnosis* / Q000235:genetics*
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