A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.
Adolescent
Biomarkers, Tumor
/ genetics
Biopsy
Child
Child, Preschool
Circulating Tumor DNA
/ analysis
DNA, Neoplasm
/ analysis
Feasibility Studies
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
/ methods
Humans
Infant
Male
Matched-Pair Analysis
Neoplasm Recurrence, Local
/ diagnosis
Neoplasms
/ blood
Pilot Projects
Precision Medicine
/ methods
Predictive Value of Tests
Transcriptome
Young Adult
Circulating tumour DNA
Clinical targeted sequencing
Paediatric oncology
Personalised medicine
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
18
04
2019
revised:
27
06
2019
accepted:
23
07
2019
pubmed:
24
9
2019
medline:
9
6
2020
entrez:
24
9
2019
Statut:
ppublish
Résumé
For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)-specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings. A total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma. We demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel-based approach can identify actionable genetic alterations in a high proportion of patients.
Sections du résumé
BACKGROUND
For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed.
METHODS
We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours. Furthermore, for a cohort of 12 patients, we used a circulating tumour DNA (ctDNA)-specific panel to sequence ctDNA from matched plasma samples and compared plasma and tumour findings.
RESULTS
A total of 255 samples were submitted from 223 patients for the NGS panel. Using FFPE tissue, 82% of all submitted samples passed quality control for clinical reporting. At least one genetic alteration was detected in 70% of sequenced samples. The overall detection rate of clinically actionable alterations, defined by modified OncoKB criteria, for all sequenced samples was 51%. A total of 8 patients were sequenced at different stages of treatment. In 6 of these, there were differences in the genetic alterations detected between time points. Sequencing of matched ctDNA in a cohort of extracranial paediatric solid tumours also identified a high detection rate of somatic alterations in plasma.
CONCLUSION
We demonstrate that tailored clinical molecular profiling of both tumour DNA and plasma-derived ctDNA is feasible for children with solid tumours. Furthermore, we show that a targeted NGS panel-based approach can identify actionable genetic alterations in a high proportion of patients.
Identifiants
pubmed: 31543384
pii: S0959-8049(19)30446-0
doi: 10.1016/j.ejca.2019.07.027
pmc: PMC6839402
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
DNA, Neoplasm
0
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
224-235Informations de copyright
Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.
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