Kidney Tumors

Discovery Dataset

The TARGET Wilms tumor (WT) project has produced comprehensive genomic profiles of nearly 130 poor outcome, clinically annotated patient cases that make up the discovery dataset. This cohort includes around 80 favorable histology Wilms tumors (FHWT) that relapsed and approximately 50 anaplastic WT cases. Each fully-characterized TARGET WT case includes data from nucleic acid samples extracted from tumor and normal tissues as follows:

• Primary tumor sample collected at diagnosis
• Normal tissue sample from peripheral blood and/or tumor adjacent normal kidney (case-matched)
• Relapsed tumor sample (case-matched) when available; some cases have 3^rd sample (those cases are considered a “trio”)

Additional cases with partial molecular characterization and/or sequencing data are available to the research community.

Case Selection Criteria

Tissues and clinical data used for the TARGET WT 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
• Unfavorable histology (anaplasia) or relapse event in favorable histology (FHWT) cases

Molecular Characterization

The TARGET KT project team relied on a variety of platforms to obtain a fully characterized dataset of nearly 130 hard to cure WT cases. 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.

Verification of Discovery Variants

The TARGET KT project team utilized a variety of sequencing approaches to confirm candidate variants identified in the discovery sample cohort as somatic. For example, mRNA-seq results are being used to determine variants that were expressed and originally identified through whole genome or exome sequencing. These verified variants will be made available as open-access data. The TARGET KT project team has additionally employed the same targeted capture sequencing approach described in the validation strategy below to verify variants seen in diagnostic tumor samples from a majority of fully-characterized patient cases in the TARGET WT discovery cohort.

Validation Strategy

Some sequence mutations identified in the poor outcome discovery cohort, along with some previously published variants, were further analyzed in an additional 550-plus cases. The TARGET KT project team employed targeted capture sequencing to look at the presence and frequency of alterations in 400 gene variants. This validation effort was performed in an unbiased cohort that was randomly selected from patients enrolled on a single COG protocol, which allowed for determination of the frequency of these changes across a broader spectrum of WT subtypes.

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.

Rhabdoid tumors (RT) are rare and very aggressive kidney tumors found mostly in young children. These patients typically have poor prognoses. TARGET researchers characterized RT genomes, transcriptomes and epigenomes through extensive second generation sequencing efforts. These data will increase understanding of the disease and facilitate the development of better therapeutic options for this tumor subtype.

Discovery Dataset

The TARGET RT subproject has produced comprehensive genomic profiles of 40 clinically annotated patient cases. Each fully-characterized TARGET RT 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 RT project were obtained from patients enrolled in renal tumor protocols 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, transcriptomic and epigenomic profiling

Molecular Characterization

The TARGET KT project team relied on a variety of sequencing platforms to obtain a fully characterized dataset of 40 RT cases. 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.

Verification & Validation of Discovery Variants

The TARGET KT project team analyzed 29 additional RT cases, using the same 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 COG renal tumor protocols (AREN03B2 or NWTS-5, like the discovery cohort). In addition, mRNA-seq results from both discovery and validation cases are being used to determine variants that 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.