Identification of de Novo Germline Mutations in the HRPT2 Gene in Two Apparently Sporadic Cases with Challenging Parathyroid Tumor Diagnoses

The diagnosis of parathyroid carcinomas is often difficult. HRPT2 mutations have been identified in familial [hyperparathyroidism-jaw tumor (HPT-JT) syndrome] and sporadic parathyroid carcinomas, supporting that HRPT2 mutations may confer a malignant potential to parathyroid tumors. In this study, we report the clinical, histopathological, and genetic investigation of two unrelated cases, whom had apparently sporadic malignant parathyroid tumors, initially diagnosed as adenomas. In one case, the differential diagnosis was complicated by cervical seeding of parathyroid tumor cells. Genetic studies identified de novo HRPT2 germline mutations in cases 1 (c.518_521delTGTC [p.Ser174LysfsX27]) and 2 (c.226 C > T [p.Arg76X]), unveiling the hereditary HPT-JT syndrome in both patients. Furthermore, the identification of somatic mutations in the patients‟ parathyroid tumors provided evidence for complete inactivation of the HRPT2 gene, which was consistent with the tumor malignant features. The sensitivity of parafibromin immunostaining to detect HRPT2 mutations was limited. The present data suggests that patients with apparently sporadic parathyroid carcinomas, or parathyroid tumors with atypical histological features, should undergo molecular genetic testing, as it may detect germline HRPT2 mutations. Establishing the diagnosis of hereditary HPT-JT syndrome is relevant for clinical counseling and management of the carriers and their relatives

Adsorption of tamoxifen on montmorillonite surface

The anticancerous drug tamoxifen is becoming a promising therapy, although some administration handicaps should be improved. Montmorillonite is a natural phyllosilicate and its use as carrier of the tamoxifen can be an interesting alternative for drug delivery system. Syntheses at different pH of montmorillonite-tamoxifen hybrids have shown promising possibilities. However, it is necessary to know the driving forces and intermolecular interactions responsible for tamoxifen adsorption on montmorillonite at different pH. Atomistic calculations of these systems have been applied based on empirical interatomic potentials. Theoretical simulations were used to explain the stoichiometry of the tamoxifen intercalation into the montmorillonite to understand the experimental behavior. The results showed there is influence on the clay structure when there is pH adjustment, with varying particle size, as well as variability in drug intercalation. Cationic species of tamoxifen was adsorbed by cation exchange mechanism and an additional adsorption of molecule as tamoxifen citrate pair also contributed in the interaction, being more energetically favorable.The authors acknowledge with gratitude the Andalusian Institute of Earth Sciences for technical support. Funding: This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil) by the Sandwich PhD Program [processo PDSE 88881.187928/2018–01] and the Spanish research project FIS2016 -77692-C2-2-P. CNPq is also acknowledged for financial support in the form of research fellowship awarded to M.G. Fonseca (grant 310921-2017-1)