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Kids First: Neuroblastoma
Kids First Data Resource
Data Resource:  Kids First Data Resource
Point of Contact:  
Allison Heath,  
Project

About This Dataset
Children with disseminated neuroblastoma have a very high risk of treatment failure and death despite receiving intensified chemotherapy, radiation therapy and immunotherapy. The long-term goal of our research program is to ultimately improve neuroblastoma cure rates by first comprehensively defining the genetic basis of the disease. The central hypothesis to be tested here is that neuroblastoma arises largely due to the epistatic interaction of common and rare heritable DNA variation. Here we will perform a comprehensive whole genome sequencing of 563 quartets of neuroblastoma patient germline and diagnostic tumor DNAs and germline DNAs from both parents. The case series was recently collected through a Children's Oncology Group epidemiology clinical trial and is robustly annotated with complete demographic (age, sex, race, ethnicity), clinical (e.g. age at diagnosis, stage, risk group), epidemiologic (parental dietary and exposure questionnaire) and biological (e.g. tumor MYCN status and multiple other tumor genomic measures) co-variates. Subjects were consented for genetic research and DNA is immediately available for shipment for sequencing. We propose Illumina-based whole genome sequencing in the 593 "trio" germline samples (Aim 1; due to missing parent: 487 full neuroblastoma triads, 106 child-single parent dyads = 1673 whole genome sequences) and matched diagnostic tumor DNA (Aim 2; N=366) at 30x sequencing depth (N=2039 whole genome sequences). Also in Aim 2 we will perform whole exome (100x) and RNA sequencing on the 366 tumor DNA and 228 tumor RNA samples from this cohort. Finally, we propose a pilot study of structural variation using long-range sequencing in 10 non-overlapping tumor samples chosen based on potentially relevant chromosomal alterations discovered with conventional NGS. Thus, a total of 2277 individual samples and 2655 sequences will be generated. We will use our established analytic pipeline that is currently being used to study the germline genomes of all cases sequenced through the NCI supported Therapeutically Applicable Research to Generate Effective Treatments program. We plan a three-stage analytic approach, first focusing on classic de novo and inherited Mendelian damaging alterations. We will next integrate our extensive epigenomic data from human neuroblastoma cell lines and genome-wide association study data (N=5,703 neuroblastoma cases to date) to guide a comprehensive assessment of noncoding variants that influence tumor initiation with a recently established analytic pipeline. Finally, we will utilize the tumor DNA analyses to inform relevance via somatic gain or loss of function effects at the sequence and/or copy number levels.
Core Data Elements
Number of Cases
1,681
Case Sex
Female (860); Male (821)
Case Age At Diagnosis
0 to 4 years (498); 5 to 9 years (11); Pediatric and Young Adult (<40 years) (1,172)
Case Race
Asian (13); Black or African American (30); Native Hawaiian or Other Pacific Islander (1); White (525); Not Reported (1,072); Unknown (37)
Case Ethnicity
Not Hispanic or Latino (567); Not Reported (1,072); Unknown (48)
Case Disease Diagnosis
Ganglioneuroma (4); Intermixed Schwannian Stroma-Rich Ganglioneuroblastoma (23); Neuroblastoma (451); Nodular Ganglioneuroblastoma (31); Other (1,172)
Case Proband
Yes (609); No (1,072)
Number of Samples
1,924
Sample Assay Method
Linked-Read Whole Genome Sequencing (12); RNA Sequencing (209); Whole Exome Sequencing (106); Whole Genome Sequencing (1,597)
Additional Data Elements
DBGAP STUDY IDENTIFIER
DATA REPOSITORY
Grant Information
X01HL136997
Published In
https://doi.org/10.1016/j.ajhg.2019.07.020
Charts
Female (860); Male (821)
860Female