Sanita Burgic
A5093751897- Neurofibromatosis and Schwannoma Cases
- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Multiple Myeloma Research and Treatments
Washington University in St. Louis
2024
Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, malignant forms PNST in the cancer predisposition syndrome, NF1.
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 NF1 PNST. Using plasma samples from novel cohort 101 patients 21 healthy controls, validated that our previous cfDNA copy number alteration (CNA)-based identifies tumor (MPNST) but cannot...
<div>AbstractPurpose:<p>Early detection of neurofibromatosis type 1 (NF1)–associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, malignant forms PNST in the cancer predisposition syndrome, NF1.</p>Experimental Design:<p>cfDNA was isolated from...
<p>Supplemental Figure 3. Number of NMF components versus AUC. Performance (AUC) models in OVO comparisons is plotted against the number n (Methods) used. The approaches AUC’s asymptote each at or before 20 components. Optimal for was defined as yielding highest AUC, area under curve; OVO, one-versus-one comparison; NMF, non-negative matrix factorization.</p>
<p>Supplemental Figure 4. 4-mer end motifs across F-profiles. Comprehensive view of the distribution and prevalence each possible motif within six distinct F-profiles derived from non-negative matrix factorization (NMF) (Methods). The analysis highlights compositions non-random nucleotides F-profiles.</p>
<p>Supplemental Figure 2. Diminishing improvements in accuracy with deeper sequencing. MPNST samples sequenced to ∼25x were downsampled five iterations per goal coverage (Methods). Size selected, copy number derived tumor fraction variability was noted between less than or equal 3x statistically significant differences (*, Welch’s T-test) 25x and below sequencing depths. No statistical difference (ns) depths greater 6x.</p>
<p>Supplemental Figure 1. Attributes of atypical neurofibroma samples. Histologic characteristics and, when available, TSO500 clinical sequencing results for paired tissue corresponding with AN cell-free DNA.</p>