A quantitative universal NGS-based ctDNA assay for hepatoblastoma

Abstract

Driver mutations in CTNNB1 are a hallmark of hepatoblastoma and offer a common biomarker for a liquid biopsy approach based on the presence of CTNNB1 circulating tumor DNA (ctDNA). We developed and investigated the utility of a quantitative universal next-generation sequencing (NGS) ctDNA assay for hepatoblastoma (QUENCH) to detect CTNNB1 ctDNA and assessed the links between ctDNA and current clinical indicators/biomarkers in hepatoblastoma. Applied to patients with hepatoblastoma, we demonstrate quantitation of various variants including single base substitutions and deletions down to 0.3% variant allele frequency, with 65% sensitivity and 100% specificity at the patient level, to allow biopsy-free tumor genotyping and sensitive ctDNA quantitation. CtDNA positivity correlates with tumor burden and ctDNA levels correlate with macroscopic residual disease and treatment response, thus providing promising evidence for the utility of quantitative ctDNA detection in hepatoblastoma.

Somatic Copy Number Alteration in Circulating Tumor DNA for Monitoring of Pediatric Patients with Cancer

“…ctDNA seems to present higher sensitivity compared to the plasma protein biomarkers (such as AFP, CEA and PSA), circulating tumor cells and miRNAs [ 29 , 35 , 36 ]. In hepatoblastomas, ctDNA was considered a more accurate indicator of disease severity and a better biomarker to track the dynamic tumor response compared to AFP [ 37 ].…”