Identification of Genomic Alterations in Sporadic Pancreatic Neurogenic Tumors.

Pancreatic neurogenic tumors, including schwannoma and neurofibroma, are rare, and their genetic aberrances have not been defined. The present study aimed at investigating the genomic alterations of pancreatic schwannoma and neurofibroma. Two patients with pancreatic schwannoma and 1 patient with neurofibroma, who underwent surgical resection at the First Affiliated Hospital, Sun Yat-sen University between June 2016 and April 2019, were recruited into the study. Their tumor tissues were analyzed by exome sequencing and genome sequencing. Exome sequencing revealed a MUTYH likely pathogenic germline variant in 1 schwannoma with somatic NF2del and NOTCH1 amplification. Pathway enrichment analysis on the other schwannoma case showed that the main abnormal function involved DNA damage repair, mitosis, and cell cycle. In addition, genome sequencing showed the inversion (INV) variant of SPIRE gene and multiple mitochondrial INV variants in both schwannoma cases. Furthermore, exome sequencing revealed NF1del, single nucleotide variation, TP53, and ERBB3 amplification in neurofibroma, whereas genomic duplication/deletion variants and mitochondrial abnormalities were much less than that in schwannoma. In conclusion, variants in NF1 and NF2 genes, amplification of key driver genes, and somatic and mitochondrial INV variants may play important roles in the development of pancreatic schwannoma and neurofibroma.