Insulinomas are functional pancreatic neuroendocrine tumors that cause hypoglycemia and severe morbidity. The aim of our study was to identify gene mutations responsible for tumorigenesis of sporadic insulinoma. Whole exome sequencing analysis was performed on tumors and paired peripheral blood from three patients with insulinomas. After initial analysis, somatic mutations were obtained and a deleterious protein product was further predicted by various bioinformatic programs. Whole exome sequencing identified 55 rare somatic mutations among three insulinoma patients, including MEN1 gene nonsense mutations (c. 681C>G; p.Tyr227* in exon 4 of MEN1 and c. 346G>T; p.Glu116* in exon 2 of MEN1) in two different tumor samples. The mutations resulted in a significant truncation of the protein and a non-functional gene product, which was involved in defective binding of menin to proteins implicated in genetic and epigenetic mechanisms. Our results extend the growing list of pathogenic MEN1 mutations in sporadic cases of insulinoma.
Keywords: MEN1; insulinoma; somatic mutation; whole exome sequencing.