Integrated multiclass driver ctDNA profiling enables MPNST detection and monitoring in NF1 patients

We developed and internally cross-validated an integrated circulating tumor DNA assay incorporating single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and structural variants (SVs) to distinguish neurofibromatosis type 1 patients with malignant peripheral nerve sheath tumors (MPNST) from those with benign plexiform neurofibromas and tumor-free controls. Among 82 participants, the assay achieved an AUC of 0.917 versus 0.737 for off-target genome-wide CNA analysis. We detected disease-specific alterations, relapse eighty days before diagnosis, and molecular clearance consistent with remission.