These tumours shed small amounts of their DNA into the patient’s bloodstream. Unlike solid tumours which are often hidden deep within a patient’s body, accessing the blood is easy and safe. Therefore, liquid biopsy - a simple blood test offering a non-invasive alternative to tissue biopsy - gives us an opportunity to detect cancer. 

Loss-of-function of the epigenetic PRC2 complex due to mutations in its core components SUZ12 or EED, is a hallmark for the transition of plexiform neurofibromas (pNF) to Malignant Peripheral Nerve Sheath Tumor (MPNST), and results in an altered DNA methylation landscape for these lesions.

This study seeks to identify DNA methylation biomarkers of MPNST, for the purpose of generating a liquid biopsy test for MPNST in NF1, in order to aid/improve the diagnosis of MPNST. DNA methylation datasets of pNF and MPNST were interrogated to identify differentially methylated regions (DMRs), and further filtering was applied based on methylation levels in blood and normal tissues known to contribute DNA to the blood, to select for DMRs suitable for MPNST classification in liquid biopsy (LB-DMRs).

LB-DMRs were combined into a signature for MPNST detection and evaluated on the bulk tissue sets to record 91-100% sensitivity and 95-100% specificity.