Novel PRUNE2 Germline Mutations in Aggressive and Benign Parathyroid Neoplasms

SIMPLE SUMMARY: Recently, PRUNE2 mutations were indicated in the pathogenesis of aggressive parathyroid neoplasms. Here, we report novel, rare PRUNE2 mutations located in exons 3, 8, 9, and 12 in patients with parathyroid tumors in the genetically homogenous Finnish population. We identified PRUNE2 mutations in patients with parathyroid carcinoma, atypical parathyroid tumors, and adenomas. While further research is needed, mutations of the PRUNE2 gene could play a role in the pathogenesis of parathyroid tumors. ABSTRACT: Parathyroid tumors are mostly sporadic but can also occur in familial forms, including different kinds of genetic syndromes with varying phenotypes and penetrance. Recently, somatic mutations of the tumor suppressor gene PRUNE2 were found to be frequent in parathyroid cancer (PC). The germline mutation status of PRUNE2 was investigated in a large cohort of patients with parathyroid tumors from the genetically homogenous Finnish population, 15 of which had PC, 16 atypical parathyroid tumors (APT), and 6 benign parathyroid adenomas (PA). Mutations in previously established hyperparathyroidism-related genes were screened with a targeted gene panel analysis. Nine PRUNE2 germline mutations with a minor allele frequency (MAF) of <0.05 were found in our cohort. Five of these were predicted to be potentially damaging and were identified in two patients with PC, two with APT, and three with PA. The mutational status was not associated with the tumor group nor related to the clinical picture or severity of the disease. Still, the frequent finding of rare germline mutations of PRUNE2 may point to the gene playing a role in the pathogenesis of parathyroid neoplasms.