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Early Detection of Malignant and Pre-Malignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Jack F. Shern, MD,  
Project

About This Dataset
Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.
Core Data Elements
Number of Cases
122
Case Sex
Female (64); Male (58)
Case Age At Diagnosis
5 to 9 years (1); 10 to 14 years (11); 15 to 19 years (18); 20 to 24 years (14); 25 to 29 years (19); 30 to 34 years (18); 35 to 39 years (10); Greater than 39 years (31)
Case Race
Not Reported (122)
Case Ethnicity
Not Reported (122)
Case Disease Diagnosis
Atypical Neurofibroma (18); Malignant Peripheral Nerve Sheath Tumor (41); Plexiform Neurofibroma (63)
Number of Samples
166
Sample Analyte Type
cfDNA (166)
Sample Anatomic Site
Unknown (166)
Sample Is Normal
Yes (21); No (145)
Additional Data Elements
DBGAP STUDY IDENTIFIER
Grant Information
1ZIABC011722-04
Genomic characterization and development of therapies for pediatric sarcoma
Published In
https://doi.org/10.1101/2024.01.18.24301053
Charts
Female (64); Male (58)
64Female