Circulating tumor DNA sequencing provides comprehensive mutation profiling for pediatric central nervous system tumors

Erin R Bonner; Robin Harrington; Augustine Eze; Miriam Bornhorst; Cassie N Kline; Heather Gordish-Dressman; Adam Dawood; Biswajit Das; Li Chen; Rini Pauly; P Mickey Williams; Chris Karlovich; Amanda Peach; D'andra Howell; James Doroshow; Lindsay Kilburn; Roger J Packer; Sabine Mueller; Javad Nazarian

doi:10.1038/s41698-022-00306-3

Circulating tumor DNA sequencing provides comprehensive mutation profiling for pediatric central nervous system tumors

NPJ Precis Oncol. 2022 Sep 6;6(1):63. doi: 10.1038/s41698-022-00306-3.

Authors

Erin R Bonner^{1

2}, Robin Harrington³, Augustine Eze¹, Miriam Bornhorst¹, Cassie N Kline⁴, Heather Gordish-Dressman⁵, Adam Dawood¹, Biswajit Das³, Li Chen³, Rini Pauly³, P Mickey Williams³, Chris Karlovich³, Amanda Peach³, D'andra Howell³, James Doroshow⁶, Lindsay Kilburn⁷, Roger J Packer⁷, Sabine Mueller^{8

9}, Javad Nazarian^{10

11

12}

Affiliations

¹ Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
² Institute for Biomedical Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³ Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁴ Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁵ Department of Biostatistics, Children's National Hospital, Washington, DC, USA.
⁶ Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic/Early Clinical Trials Development Program, National Cancer Institute, Bethesda, MD, USA.
⁷ Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
⁸ Department of Neurology, Neurosurgery and Pediatrics, University of California San Francisco, San Francisco, CA, USA.
⁹ Department of Pediatrics, University Children's Hospital Zürich, Zürich, Switzerland.
¹⁰ Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA. [email protected].
¹¹ Institute for Biomedical Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. [email protected].
¹² Department of Pediatrics, University Children's Hospital Zürich, Zürich, Switzerland. [email protected].

Abstract

Molecular profiling of childhood CNS tumors is critical for diagnosis and clinical management, yet tissue access is restricted due to the sensitive tumor location. We developed a targeted deep sequencing platform to detect tumor driver mutations, copy number variations, and heterogeneity in the liquid biome. Here, we present the sensitivity, specificity, and clinical relevance of our minimally invasive platform for tumor mutation profiling in children diagnosed with CNS cancer.

Abstract

Grants and funding