Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA

Area of Science:

• Pediatric Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Neuroblastoma (NB) is an aggressive childhood cancer.
• High-risk NB (HRNB) requires intensive treatment based on tumor genetics.
• Current risk stratification relies on invasive surgical biopsies.

Purpose of the Study:

• To evaluate the utility of circulating tumor DNA (ctDNA) for detecting genetic alterations in NB.
• To identify actionable biomarkers in NB patients using a non-invasive liquid biopsy approach.

Main Methods:

• Targeted next-generation sequencing (tNGS) of a 42-gene panel was used on 32 NB ctDNA samples.
• Droplet digital PCR was employed to detect specific ALK variants.
• Analysis focused on single-nucleotide variants and copy number changes.

Main Results:

• Pathogenic mutations (VAF > 1%) were found in 41% (13/32) of ctDNA samples.
• ALK and PTPN11 mutations were the most frequent (13% each), alongside oncogene amplifications.
• Actionable variants, including those missed in primary tumors due to heterogeneity, were detected.

Conclusions:

• ctDNA analysis is a valuable tool for detecting genetic abnormalities in neuroblastoma.
• This non-invasive method can identify actionable variants, aiding in risk assessment and treatment selection for NB.
• ctDNA profiling holds promise for overcoming challenges posed by tumor heterogeneity.