Atypical Neurofibromas reveal distinct epigenetic features with proximity to benign peripheral nerve sheath tumor entities

Unsupervised hierarchical clustering and t-SNE analysis indicated that 36/40 ANF cluster separately from MPNST and instead close to the benign tumor entities. Of these 36 tumors, 23 ANF formed a molecularly distinct cluster in proximity to schwannomas. Tumors from this cluster had frequent heterozygous or homozygous loss of CDKN2A/B and significantly more lymphocyte infiltration than MPNST, schwannomas, and NF. Few ANF clustered closely with neurofibromas, schwannomas, or MPNST, raising the question, whether diagnosis based on histological features alone might pose a risk to both over- and underestimate the aggressiveness of these lesions. 40 samples of histologically diagnosed atypical neurofibromas, ANNUBPs and low grade MPNST from 40 individuals were analyzed. All samples passed the detection p-value cut-off of <0.01.