In the expansion effort, TARGET investigators analyzed tumors from pediatric patients, most who experienced an early bone marrow relapse (within 4 years of initial diagnosis), to identify new therapeutic approaches and/or biomarkers that correlate with poor clinical outcome to treat childhood pre-cursor B-cell ALL. The tissues used in this study were collected from patients enrolled in Children's Oncology Group (COG) biology studies and clinical trials.
The ALL project team members (like other TARGET researchers) have generated data in two phases: Discovery and Validation. Visit the TARGET Research page to learn more.
Discovery Dataset
The TARGET ALL Phase II project has produced comprehensive genomic profiles of nearly 200 relapse-enriched, clinically annotated patient cases in the discovery dataset. This cohort includes more than 100 patients with adequate relapse specimens to study as trios (see three sample types below). Each fully-characterized TARGET ALL case includes data from nucleic acid samples extracted from peripheral blood or bone marrow tissues as follows:
- Primary tumor sample collected at diagnosis
- Case-matched tissue sample collected at remission (FACS purified, <5% blasts detected following standard induction therapy)
- Relapsed tumor sample (case-matched) when available; >50% cases have 3rd 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 ALL Phase II project were obtained from patients enrolled on biology studies and clinical trials managed through the Children’s Oncology Group (COG). Patient samples with full characterization were chosen based on the following criteria:
- Experienced early bone marrow relapse (< 4 years from time of diagnosis)
- Adequate amount of high-quality nucleic acids for comprehensive genomic profiling
Molecular Characterization
The TARGET ALL project team relied on a variety of platforms to obtain a fully characterized dataset of ~200 relapse-enriched cases. The COG ALL 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.
| General Methodology |
Platform |
|---|
| Clinical Annotation |
COG Protocols (AALL03B1, AALL0232, P9906, AALL0331, ALL0434) |
| Gene Expression |
Affymetrix U133 Plus 2.0 Array |
| Chromosome Copy Number Analyses & Loss of Heterozygosity |
Affymetrix SNP 6.0 Array |
| Epigenetics (DNA Methylation) |
HELP Assay |
| Whole Genome Sequencing |
Complete Genomics Incorporated |
| Whole Exome Sequencing |
Illumina Hi-Seq 2000 |
| mRNA-seq |
Illumina Hi-Seq 2000 |
| miRNA-seq |
Illumina Hi-Seq 2000 |
Verification of Discovery Variants
The TARGET ALL 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 which were expressed and originally identified through whole genome or exome sequencing. These verified variants will be made available as open-access data.
Validation Strategy
To validate sequence mutations identified in the relapse-enriched discovery cohort, along with some previously published variants in adult ALL, an additional 750 cases were further analyzed. The TARGET ALL project team employed whole exome sequencing to look at the frequency of these changes across a broader spectrum of ALL subtypes in an unbiased cohort of 500 precursor B-cell ALL and 250 T-cell lineage ALL cases. Patients were enrolled on a single COG protocol and selected for inclusion in the validation effort if DNA were available.
All data from the discovery cohort and this validation effort are made available as specified in the Using TARGET Data and TARGET Publication Guidelines pages. The TARGET Data Matrix provides an overview of the data generated and described above.
