Abstract 2251: Gene expression analysis by RNA-sequencing highlights differential regulated pathways involved in cell cycle and inflammation in orbitofacial neurofibromas

Abstract

Abstract Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. Orbitofacial NFs in particular may cause progressive, disfiguring tumors of the lid, brow, temple, face and orbit, and anecdotal evidence suggest that they may have increased local aggressiveness compared to NFs developing at other sites. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We performed global RNA-sequencing in orbitofacial (n=10) and non-orbitofacial (n=9) NFs. A total of 880 mRNA transcripts were differentially expressed between the two groups (adjusted p>0.05), The top 10 genes relatively overexpressed in orbitofacial NF included NEFL, TREM2, CST1, GAP43, ADORA3, MIA, SYT6, FCGR3A, SPP1, and FCGR1A. The top 10 genes relatively underexpressed in orbitofacial NF included XG, WISP2, MMP27, CXCL14, MFAP5, APLNR, MYOC, SLITRK6, STMN2, and TDRD1. Gene enrichment analyses demonstrated a variety of gene sets differentially affected including pathways involved in cell proliferation, interferon and immune related pathways. Comparisons with publicly available databases of various Schwann cell tumors and models using CAT plots demonstrated the highest overlap with differentially expressed genes in plexiform NF vs MPNST (>10%). In summary, we identified gene expression differences between orbitofacial NF and NFs occurring at other anatomic locations. Further investigation may be warranted, given that orbitofacial NF are notoriously difficult to treat and associated with disproportionate morbidity. Citation Format: Eddie L. Imada, Deepak P. Edward, Antje Arnold, Hailah Al-Hussain, Diego Strianese, Luigi Marchionni, Fausto J. Rodriguez. Gene expression analysis by RNA-sequencing highlights differential regulated pathways involved in cell cycle and inflammation in orbitofacial neurofibromas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2251.