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

doi:10.1371/journal.pone.0062233

DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors

PLoS One. 2013 Apr 26;8(4):e62233. doi: 10.1371/journal.pone.0062233. Print 2013.

Authors

Hitomi Ueno¹, Hajime Okita, Shingo Akimoto, Kenichiro Kobayashi, Kazuhiko Nakabayashi, Kenichiro Hata, Junichiro Fujimoto, Jun-Ichi Hata, Masahiro Fukuzawa, Nobutaka Kiyokawa

Affiliation

¹ Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Cluster Analysis
CpG Islands / genetics
DNA Methylation / genetics*
Diagnosis, Differential
Genes, Neoplasm / genetics
Humans
Kidney / metabolism
Kidney / pathology
Kidney Neoplasms / diagnosis*
Kidney Neoplasms / genetics*
Restriction Mapping
Sarcoma, Clear Cell / diagnosis*
Sarcoma, Clear Cell / genetics*

Grants and funding

This work was supported by Health and Labour Sciences Research Grants (the 3rd-term comprehensive 10-year strategy for cancer control H22-011), Grant-in-Aid for Scientific Research (B)(23390405, Grant of National Center for Child Health and Development (22A-5, 24-4), and Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO, 10-41, -42, -43, -44, -45). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.