A Targeted Gene Panel for Circulating Tumor DNA Sequencing in Neuroblastoma

被引:22
作者
Cimmino, Flora [1 ]
Lasorsa, Vito Alessandro [1 ,2 ]
Vetrella, Simona [3 ]
Iolascon, Achille [1 ,2 ]
Capasso, Mario [1 ,2 ]
机构
[1] CEINGE Biotecnol Avanzate, Naples, Italy
[2] Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy
[3] Santobono Pausilipon Childrens Hosp, Dept Pediat Oncol, Naples, Italy
关键词
genetic mutation; bioinformactics analysis; next generation sequencing; neuroblastoma; liquid biopsy and circulating tumor DNA; CELL-FREE DNA; READ ALIGNMENT; LIQUID BIOPSY; HETEROGENEITY; RESISTANCE; MUTATIONS; LANDSCAPE; PATHWAY; GENOME; TISSUE;
D O I
10.3389/fonc.2020.596191
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 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 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 ad hoc bioinformatic analyses including the hard filtering of the variant calls. Results We identified 9/11 (81.8%) patients who carry at least one pathogenic variation. The most frequently mutated genes were KMT2C (five cases), NOTCH1/2 (four cases), CREBBP (three cases), ARID1A/B (three cases), ALK (two cases), FGFR1 (two cases), FAT4 (two cases) and CARD11 (two cases). 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.
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页数:9
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