Neuroblastoma

TARGET investigators are analyzing tumors from pediatric patients to identify biomarkers that correlate with poor clinical outcome and/or new therapeutic approaches to treat childhood Neuroblastoma (NBL). The tissues used in this study were collected from patients enrolled in Children's Oncology Group (COG) biology studies and clinical trials.

The TARGET Neuroblastoma project team members (like other TARGET researchers) are generating data in two phases: Discovery and Validation. Visit the TARGET Research page to learn more.

Discovery Dataset

The TARGET neuroblastoma (NBL) project has produced comprehensive genomic profiles of more than 200 clinically annotated patient cases within the discovery dataset. This cohort includes nearly 200 high-risk patient cases, including some who have relapsed and subsets of low-risk and/or stage 4S NBL cases (tumors that spontaneously regress without treatment). Each fully-characterized TARGET NBL 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 or bone marrow (case-matched)
• Relapsed tumor sample (case-matched) when available; some cases have 3^rd sample (those cases are considered a “trio”)

There are a large number of additional cases, varying in risk level, with partial molecular characterization and/or sequencing data that are available to the research community.

Case Selection Criteria

Tissues and clinical data used for the TARGET NBL 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:

• Tumor cellularity of >70% in tumor specimens and tumor necrosis of <30%
• High-quality nucleic acids in amounts adequate to complete comprehensive genomic profiling
• Preference for high-risk cases (Stage 4) who have relapsed or whose tumors spontaneously regress without treatment (Stage 4S)

Molecular Characterization

The TARGET NBL project team relied on a variety of platforms to obtain a fully characterized dataset of more than 200 cases. The COG NBL 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 NBL 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

Some sequence mutations identified in the discovery cohort, along with some previously published variants, were further analyzed in an additional 500 cases. The TARGET NBL 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 NBL subtypes.

All data from the discovery and validation efforts 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.

The TARGET NBL Project team consists of COG investigators at various institutions who work together with the scientists, analysts, project managers and technicians from the COG (Biorepository, Data and Statistics Core) and NCI offices (Office of Cancer Genomics, Clinical Therapy Evaluation Program, Center for Cancer Research and Center for Bioinformatics and Information Technology). This collaborative network is led by the following:

Principal Investigator

• John M. Maris, M.D.
  • Children's Hospital of Philadelphia

Co-Principal Investigator

• Robert Seeger, M.D.
  • Children's Hospital of Los Angeles

NCI Intramural Lead Investigator

• Javed Khan, M.D.
  • National Cancer Institute, Center for Cancer Research

• Wei JS, Kuznetsov IB, Zhang S, et al. Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk MYCN-Not-Amplified Human Neuroblastoma. Clin Cancer Res. 2018 Nov 15;24(22):5673-5684. (PMID: 29784674) View PubMed abstract
• Oldridge DA, Wood AC, Weichert-Leahey N, et al. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature. 2015 Dec 17;528(7582):418-21. (PMID: 26560027) View PubMed abstract
• Eleveld TF, Oldridge DA, Bernard V, et al. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet. 2015 Aug;47(8):864-71. (PMID: 26121087) View PubMed abstract
• Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet. 2013 Mar;45(3):279-84. (PMID: 23334666) View PubMed abstract