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Updated: Sep 17, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric
Marian H Harris1, Steven G DuBois2, Julia L Glade Bender3
1Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
Importance:
Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit.
Objective:
To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors.
Design, Setting, And Participants:
Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high-risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014.
Interventions:
Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available.
Main Outcomes And Measures:
Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations.
Results:
Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome and translocations suggesting a change in diagnosis. In total, 43 (43% [95% CI, 33%-53%]) participants had results with potential clinical significance.
Conclusions And Relevance:
A multi-institution clinical genomics study in pediatric oncology is feasible and a substantial proportion of relapsed or refractory pediatric solid tumors have actionable alterations.
Trial Registration:
clinicaltrials.gov Identifier: NCT01853345.
Insights
Clinical sequencing is feasible in pediatric oncology, identifying actionable alterations in a significant portion of relapsed or refractory solid tumors. This approach aids in personalized cancer therapy (iCat) recommendations for young patients.
Area of Science:
- Pediatric Oncology
- Cancer Genomics
- Precision Medicine
Background:
- Pediatric cancers have low mutation frequencies and limited targeted therapies, making the benefit of clinical sequencing uncertain.
- Identifying actionable genomic alterations is crucial for advancing precision medicine in pediatric oncology.
Purpose of the Study:
- To evaluate the feasibility of identifying actionable genomic alterations in pediatric patients with extracranial solid tumors.
- To assess the utility of individualized cancer therapy (iCat) recommendations based on clinical sequencing results.
Main Methods:
- A multi-institution clinical sequencing study involving 100 pediatric patients (≤30 years) with high-risk, recurrent, or refractory extracranial solid tumors.
- Tumor profiling included mutation detection (Sequenom assay or targeted next-generation sequencing) and copy number assessment (array comparative genomic hybridization).
- Results were reviewed by a multidisciplinary panel to generate iCat recommendations when actionable alterations and available therapies were identified.
Main Results:
- Clinical sequencing was technically successful in 89% of participants.
- 31% of patients received an individualized cancer therapy (iCat) recommendation, with 3 receiving matched therapy.
- Common actionable alterations involved cancer-associated signaling pathway genes, MYC/MYCN copy number alterations, and cell cycle genes. Overall, 43% had results with potential clinical significance.
Conclusions:
- A multi-institution clinical genomics study is feasible in pediatric oncology.
- A substantial proportion of relapsed or refractory pediatric solid tumors harbor actionable genomic alterations.
- Clinical sequencing can provide valuable information for guiding treatment decisions in pediatric cancer patients.
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