Circulating free DNA in the plasma of individuals with neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome whose characteristic manifestations include benign neurofibromas, yet NF1 is also associated with a high risk of cancer. Measurements of circulating free plasma DNA (cfDNA) are gaining wider applicability in cancer diagnostics, targeting of therapy, and monitoring of therapeutic response. Individuals with NF1 are likely to be followed up using this method, but the effects of NF1 and neurofibromas on cfDNA levels are not known. We studied peripheral blood samples from 19 adults with NF1 and 12 healthy controls. The cfDNA was isolated from plasma with QIAamp Circulating Nucleic Acid Kit and quantified using the Qubit 2.0 Fluorometer. The cfDNA concentration of each sample was normalized relative to the plasma protein concentration. The normalized median concentration of cfDNA in plasma was 19.3 ng/ml (range 6.6–78.6) among individuals with NF1 and 15.9 ng/ml (range 4.8–47.0) among controls (p = .369). Individuals with NF1 who also had plexiform neurofibroma (pNF) showed non‐significantly elevated cfDNA concentration compared to individuals with NF1 and without known pNF (median 25.4 vs. 18.8 ng/ml, p = .122). The effect of NF1 on cfDNA seems to be relatively small and NF1 is therefore unlikely to hamper the use of cfDNA‐based assays.

Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials

“…22 Although the application of this technology to cancer predispositions and rare disease has been recent, its potential has been quickly realized. For example, since the first publication in 2021 applying cfDNA to NF1, 17 at least four additional publications have described the application of circulating DNA in NF1 17,24,25 (Table 1).…”

Is rheumatoid arthritis a neglected comorbidity in neurofibromatosis type 1?

“…Thus, free DNA can be detected in NF-1 patients and systemic autoimmune diseases. 19,20 RA is known to be the most prevalent cause of chronic autoimmune inflammatory arthritis, developing as a result of the complex interactions of genes and environmental factors and ending up with an impaired immune tolerance and synovial inflammation in characteristic symmetrical joints. 21 Besides, the literature host two interesting case reports pointing to the association of RA and NF-1.…”

The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples

“…Several manufacturers, such as Qiagen, Norgen, Thermo, and Promega, produce specialized commercial kits for extracting blood-derived cfDNA ( Diefenbach et al, 2018 ; van Dessel et al, 2019 ; Huebner et al, 2021 ; Wang et al, 2021 ). Among these, Qiagen’s systematic kits are the most commonly used ( Vermeulen et al, 2017 ; Jain et al, 2019 ; Jiang et al, 2020 ; Kallionpaa et al, 2021 ), However, comparing the performance of these kits is challenging due to variations in sample collection, processing, and analysis procedures ( Table 5 ). For example, when PCR is used to quantify specific genes, the sensitivity may decrease or even vanish as cfDNA fragments become shorter ( Ungerer et al, 2020 ).…”