A Targeted Gene Panel for Circulating Tumor DNA Sequencing in Neuroblastoma.
bioinformactics analysis
genetic mutation
liquid biopsy and circulating tumor DNA
neuroblastoma
next generation sequencing
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
08
2020
accepted:
27
10
2020
entrez:
31
12
2020
pubmed:
1
1
2021
medline:
1
1
2021
Statut:
epublish
Résumé
Liquid biopsies do not reflect the complete mutation profile of the tumor but have the potential to identify actionable mutations when tumor biopsies are not available as well as variants with low allele frequency. Most retrospective studies conducted in small cohorts of pediatric cancers have illustrated that the technology yield substantial potential in neuroblastoma. The molecular landscape of neuroblastoma harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to characterize the mutational landscape of primary neuroblastoma using a custom gene panel for ctDNA targeted sequencing. Targeted next-generation sequencing (NGS) was performed on ctDNA of 11 patients with primary neuroblastoma stage 4. To avoid the detection of false variants, we used UMIs (unique molecular identifiers) for the library construction, increased the sequencing depth and developed We identified 9/11 (81.8%) patients who carry at least one pathogenic variation. The most frequently mutated genes were We developed a targeted NGS approach to identify tumor-specific alterations in ctDNA of neuroblastoma patients. Our results show the reliability of our approach to generate genomic information which can be integrated with clinical and pathological data at diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
Liquid biopsies do not reflect the complete mutation profile of the tumor but have the potential to identify actionable mutations when tumor biopsies are not available as well as variants with low allele frequency. Most retrospective studies conducted in small cohorts of pediatric cancers have illustrated that the technology yield substantial potential in neuroblastoma.
AIM
OBJECTIVE
The molecular landscape of neuroblastoma harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to characterize the mutational landscape of primary neuroblastoma using a custom gene panel for ctDNA targeted sequencing.
METHODS
METHODS
Targeted next-generation sequencing (NGS) was performed on ctDNA of 11 patients with primary neuroblastoma stage 4. To avoid the detection of false variants, we used UMIs (unique molecular identifiers) for the library construction, increased the sequencing depth and developed
RESULTS
RESULTS
We identified 9/11 (81.8%) patients who carry at least one pathogenic variation. The most frequently mutated genes were
CONCLUSIONS
CONCLUSIONS
We developed a targeted NGS approach to identify tumor-specific alterations in ctDNA of neuroblastoma patients. Our results show the reliability of our approach to generate genomic information which can be integrated with clinical and pathological data at diagnosis.
Identifiants
pubmed: 33381456
doi: 10.3389/fonc.2020.596191
pmc: PMC7769379
doi:
Types de publication
Journal Article
Langues
eng
Pagination
596191Informations de copyright
Copyright © 2020 Cimmino, Lasorsa, Vetrella, Iolascon and Capasso.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AC declared a past co-authorship with several of the authors SV, VAL, MC to the handling editor.
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