Gabriella Miller Kids First Pediatric Research Program: An Integrated Clinical and Genomic Analysis of Treatment Failure in Pediatric Osteosarcoma

The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the genomic and phenotypic data from this study are accessible through dbGaP. The data is also available at the Kids First Portal, where other Kids First datasets can also be accessed in the cloud for data analysis, data visualization, collaboration and interoperability, open to all researchers and developers.

Although the survival of children with relapsed osteosarcoma is very poor, little is known about the etiology of treatment failure in this disease. The purpose of this project is to perform whole genome sequencing on serial samples from patients with osteosarcoma obtained before treatment, after treatment, and at relapse/metastasis in order to identify the mutations and pathways that are drivers of drug resistance. If successful, our results may help identify patients at high risk for treatment failure and may yield new treatments for children who cannot currently be cured.

• Study Weblinks:
  • Gabriella Miller Kids First
• Study Design:
  • Tumor vs. Matched-Normal
• Study Type:
  • Tumor vs. Matched-Normal
• Total number of consented subjects: 84
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample

Germline, pre-treatment primary tumor, post-treatment primary tumor, relapse, and metastasis samples and clinical data from 123 patients were selected for whole genome sequencing and whole transcriptome sequencing from seven collaborating US institutions as part of Gabriella Miller Kids First Osteosarcoma project.

For the past thirty years, despite intense effort, there has been no improvement in outcome for children with osteosarcoma (OS). In particular, for the roughly 40% of OS patients who experience disease relapse and the 30% of OS patients with metastases, the 5-year overall survival remains a dismal 23% and 35%, respectively.

The purpose of this study is to test the hypothesis that we can identify the genetic drivers of drug resistance, relapse, and metastasis in OS by serially following the evolution of clones within a single patient from germline to diagnosis to residual tumor following chemotherapy, to relapse or metastasis. To obtain significant insights into mechanisms of oncogenesis and the emergence of drug resistant or metastatic clones, we have recruited large number of osteosarcoma cases from collaborating with seven US institutions.

For the current Kids First project whole genome sequencing and whole transcriptome sequencing will be performed in 123 patients with Osteosarcoma.

• Primary Phenotype: Osteosarcoma

• Principal Investigator
  • Kenan Onel, MD, PhD. Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY, USA.
• Funding Source
  • X01 HL132378. National Institutes of Health, Bethesda, MD, USA.