# Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA

## TL;DR

This study shows that ctDNA from blood can detect genetic mutations in neuroblastoma, offering a non-invasive alternative to biopsies.

## Contribution

The study demonstrates that ctDNA can detect actionable genetic variants in neuroblastoma, including those missed by primary tumor biopsies.

## Key findings

- Pathogenic mutations with VAF > 1% were found in 41% of ctDNA samples.
- ALK and PTPN11 mutations were each detected in 13% of samples.
- ctDNA detected variants absent in primary tumors due to tumor heterogeneity.

## Abstract

Neuroblastoma (NB) is an aggressive childhood cancer requiring intensive multimodal therapies in high-risk (HRNB) patients. Currently, invasive surgical biopsies are required to classify NB risk group and assign treatment based on the tumour genetic profile. Circulating tumour DNA (ctDNA) obtained from blood samples can be used to identify tumour biomarkers. Here we applied targeted next-generation sequencing (tNGS) using a panel of 42 genes to analyse 32 NB ctDNA samples for the presence of single-nucleotide variants and copy number changes from 28 patients in all NB risk groups. In two additional ctDNA samples, droplet digital PCR was used to detect hotspot ALK variants. Pathogenic mutations with a variant allele frequency (VAF) > 1% were identified in 13/32 (41%) ctDNA samples. ALK and PTPN11 were the most frequent, each being detected in 4/32 (13%) samples, together with oncogene amplifications. Targeted NGS of ctDNA detected actionable variants, including those absent in the diagnostic primary tumour due to spatial and temporal heterogeneity. Our findings confirm the usefulness of ctDNA in detecting genetic abnormalities in NB.