Clinical utility of custom-designed NGS panel testing in pediatric tumors

BACKGROUND: Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers. METHODS: Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed. RESULTS: NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration. CONCLUSIONS: Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.

Abstract licence: CC BY-NC-ND

1. 33.

   Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations · 2016

2. 39.

   Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden · 2017

3. 50.

   Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours · 2018

52 more references, whose wording the paper’s licence keeps private.

• Pediatric low-grade glioma in the era of molecular diagnostics · 2020

• Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network · 2020

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.