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

We developed and cross-validated an integrated circulating tumor DNA assay incorporating SNVs, indels, CNAs, and SVs to distinguish neurofibromatosis type 1 patients with malignant peripheral nerve sheath tumors from those with benign plexiform neurofibromas or tumor-free controls. Among 82 participants, the assay achieved an AUC of 0.904, compared with 0.735 for genome-wide CNAs. We also detected recurrent disease-specific driver alterations, relapse up to three months before diagnosis, and early clearance consistent with durable remission.