TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney

Oncotarget. Volume 6, Issue 18: p.15828-15841, 30 June 2015, 10.18632/oncotarget.4682

Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified. One tumor with t(10;17)(q22;p13) involving fusion of YHWAE with NUTM2B was identified. Integrated analysis of expression and methylation data identified promoter hypermethylation and low expression of the tumor suppressor gene TCF21 (Pod-1/capsulin/epicardin) in all CCSKs except the case with t(10;17)(q22;p13). TARID, the long noncoding RNA responsible for demethylating regulatory CpGs around the TCF21 locus, was virtually undetectable in most CCSKs. TCF21 hypermethylation and decreased TARID expression were validated in an independent set of 19 CCSK tumor samples (data not submitted). The presence of significant hypermethylation of TCF21, a transcription factor known to be active early in renal development, supports the hypothesis that hypermethylation of TCF21 and/or decreased TARID expression lies within the pathogenic pathway of most CCSKs. Future studies are needed to functionally verify a tumorigenic role of TCF21 down-regulation and to tie this to the unique gene expression pattern of CCSK.

This study characterized TARGET cases as described below:

GE=gene expression; CN=copy number

In order to access Controlled TARGET CCSK data using the links below, users must submit an application for Authorized Access via dbGaP as described on dbGaP’s TARGET Study Page. To begin the application process, please view the information and instructions provided on the dbGaP Authorized Access Login Page under “dbGaP Data Download”.

Supplemental Data Files

• GDC Manifests
  • Controlled-Access Data Download Manifest (6 Files)
  • Open-Access Data Download Manifest (16 Files)
  • WGS CGI Files Download Manifest (13 Files)

• Copy Number Array
  • TARGET CCSK Copy Number Array Level 1 Data (Controlled)
  • TARGET CCSK Copy Number Array Level 2 Data (Controlled)
  • TARGET CCSK Copy Number Array Level 3 Data
  • TARGET CCSK Copy Number Array Metadata
• Gene Expression Array
  • Gene Expression Array Level 1 Data
  • Gene Expression Array Level 2 Data
  • Gene Expression Array Level 3 Data
  • Gene Expression Array Metadata
• Methylation Array
  • TARGET CCSK Methylation Array Level 1 Data (Controlled)
  • TARGET CCSK Methylation Array Level 2 Data
  • TARGET CCSK Methylation Array Level 3 Data
  • TARGET CCSK Methylation Array Metadata
• mRNA-Seq
  • TARGET CCSK mRNA-Seq Level 3 Data
  • TARGET CCSK mRNA-Seq Level 3 Data (Controlled)
  • TARGET CCSK mRNA-Seq Metadata
• WGS
  • TARGET CCSK WGS Level 3 Data
  • TARGET CCSK WGS Level 3 Data (Controlled)
  • TARGET CCSK WGS Level 4 Data
  • TARGET CCSK WGS Metadata
• Miscellaneous Files
  • TARGET CCSK Sample Matrices
  • TARGET CCSK CGI Requested Reports (Controlled)

Additional Resources

• SRA - SRP012000 (link is external) NCBI

Instructions for Data Download

Open Access Data

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2. Use the manifest file to download data using the GDC Data Transfer Tool (DTT) or the GDC API
   • GDC DTT (Download, User's Guide)
   • GDC API (User’s Guide)

Controlled Access Data

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2. Download a token from the GDC Data Portal
   • GDC Data Portal (Launch, User’s Guide)
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   • GDC DTT (Download, User’s Guide)
   • GDC API (User’s Guide)

For assistance, please contact the GDC Help Desk: support@nci-gdc.datacommons.io