Banerjee_NFYIF_2022.pdf

Neurofibromatosis type 1 (NF1) is a cancer predisposing syndrome affecting 1 in 3000 people, with diverse clinical manifestations including benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs). In 10% of cases, plexiform neurofibromas show nuclear and cellular abnormalities that accompany progression towards malignancy. Once they transform into MPNSTs, therapeutic options become severely limited leading to a 5-year survival rate of 30%. While mutations in various genes like CDKN2A, TP53, SUZ12, and EED may indicate completed transformation to MPNST, very few early genetic events characterize transition from PN to MPNST. Additionally, cis-regulation of expression in protein coding genes have been studied extensively, but little is known about the trans-regulation of gene expression via microRNAs (miRNAs) in PNs and MPNSTs. We hypothesize that the early genomic instability that accompanies malignant transformation of PNs to MPNSTs causes mutations in miRNA genes and that these mutations could act as early indicators of transformation. We aim to identify genomic variants in critical domains of miRNA genes that are key differentiators between MPNSTs and PNs.