Integrated Multiclass Driver ctDNA Profiling Enables MPNST Detection and Monitoring in NF1 Patients.
Paul A Jones, Aaron U Bektas, Jeffrey J Szymanski, R Taylor Sundby, John S A Chrisinger, Peter K Harris, Mark I Zoberi, Kara Weekley, Sanita Burgic, Stacey Chamberlain, Faridi Qaium, Jack F Shern, Aadel A Chaudhuri, Angela C Hirbe
Abstract
Open AccessWe 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.