DNA Methylation Profile Distinguishes Clear Cell Sarcoma of the Kidney from Other Pediatric Renal Tumors

Hitomi Ueno, Hajime Okita, Shingo Akimoto, Kenichiro Kobayashi, Kazuhiko Nakabayashi, Kenichiro Hata, Junichiro Fujimoto, Jun ichi Hata, Masahiro Fukuzawa, Nobutaka Kiyokawa

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article numbere62233
JournalPLoS One
Volume8
Issue number4
DOIs
Publication statusPublished - 2013 Apr 26
Externally publishedYes

Fingerprint

Clear Cell Sarcoma
Pediatrics
sarcoma
DNA methylation
DNA Methylation
Tumors
kidneys
Kidney
neoplasms
Neoplasms
cells
Mesoblastic Nephroma
Nephroma
Rhabdoid Tumor
Ewing's Sarcoma
Wilms Tumor
Sarcoma
bisulfites
DNA Fingerprinting
Epigenomics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

DNA Methylation Profile Distinguishes Clear Cell Sarcoma of the Kidney from Other Pediatric Renal Tumors. / Ueno, Hitomi; Okita, Hajime; Akimoto, Shingo; Kobayashi, Kenichiro; Nakabayashi, Kazuhiko; Hata, Kenichiro; Fujimoto, Junichiro; Hata, Jun ichi; Fukuzawa, Masahiro; Kiyokawa, Nobutaka.

In: PLoS One, Vol. 8, No. 4, e62233, 26.04.2013.

Research output: Contribution to journalArticle

Ueno, H, Okita, H, Akimoto, S, Kobayashi, K, Nakabayashi, K, Hata, K, Fujimoto, J, Hata, JI, Fukuzawa, M & Kiyokawa, N 2013, 'DNA Methylation Profile Distinguishes Clear Cell Sarcoma of the Kidney from Other Pediatric Renal Tumors', PLoS One, vol. 8, no. 4, e62233. https://doi.org/10.1371/journal.pone.0062233
Ueno, Hitomi ; Okita, Hajime ; Akimoto, Shingo ; Kobayashi, Kenichiro ; Nakabayashi, Kazuhiko ; Hata, Kenichiro ; Fujimoto, Junichiro ; Hata, Jun ichi ; Fukuzawa, Masahiro ; Kiyokawa, Nobutaka. / DNA Methylation Profile Distinguishes Clear Cell Sarcoma of the Kidney from Other Pediatric Renal Tumors. In: PLoS One. 2013 ; Vol. 8, No. 4.
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