Clear cell sarcoma of the kidney (CCSK) is a rare kidney tumor that usually occurs in children age 3 or younger. Although treatment outcomes are generally favorable, patients undergo highly toxic therapies, which can lead to complications later in life (e.g., additional cancers or infertility). As CCSK is uncommon, the lack of tumor tissues for research makes studying the underlying biology of the disease difficult. The TARGET Kidney Tumors (KT) project team analyzed tumors from pediatric CCSK patients using a comprehensive, integrated genomic approach to identify new therapeutic approaches and/or biomarkers that correlate with poor clinical outcome.
The TARGET CCSK subproject has produced comprehensive genomic profiles of 13 clinically annotated patient cases. Each fully-characterized TARGET CCSK case consists of data generated from nucleic acid samples extracted from case-matched tumor and normal tissues as follows:
- Primary tumor sample collected at diagnosis
- Normal tissue sample from peripheral blood or tumor adjacent normal kidney (case-matched)
Case Selection Criteria
Tissues and clinical data used for the TARGET CCSK project were obtained from patients enrolled in the National Wilms Tumor Study (mostly NWTS-5) clinical trial that is now run through the Children's Oncology Group (COG). Patient samples with full characterization were chosen based on the following criteria:
- Tumor cellularity of >80% in tumor specimens and tumor necrosis of <20%
- High-quality nucleic acids in amounts adequate to complete comprehensive genomic profiling
- Relapse event (~50 patient cases studied)
The TARGET KT project team relied on a variety of platforms to obtain a fully characterized dataset of 13 CCSK cases, including some who have relapsed. The COG renal tumors Statistics and Data Center provided clinical annotations and outcome data for all cases. Visit the TARGET Project Experimental Methods page for detailed information and protocols.
||Affymetrix U133 Plus 2.0 Array
|Chomosome Copy Number Analyses & Loss of Heterozygosity
||Affymetrix SNP 6.0 Array
|Epigenetics (DNA Methylation)
||Illumina Infinium 450K
|Whole Genome Sequencing
||Complete Genomics Incorporated
||Illumina Hi-Seq 2000
Verification & Validation of Discovery Variants
The TARGET KT project team analyzed 9 additional CCSK cases, using the molecular profiling and sequencing approaches described above (see table), to confirm the presence and frequency of candidate variants found in the discovery dataset. This validation effort was performed in an unbiased cohort that was selected based on availability of tissue from patients enrolled on a single protocol (NWTS-5, like the discovery cohort; cases were chosen without regard for relapse). In addition, mRNA-seq results from both discovery and validation cases are being used to determine variants which were expressed and originally identified through whole genome sequencing. These verified variants will be made available as open-access data.
All data from the discovery cohort and this validation effort are available through the TARGET Data Matrix. These data must be used as specified in the TARGET Publication Guidelines.