Molecular analysis of the HPJ-JT syndrome and sporadic parathyroid carcinogenesis

Abstract

HPT-JT syndrome is a rare disease characterized by parathyroid tumours (with a high percentage of carcinomas), jaw and kidney tumours. In this thesis, the clinical and genetic features of the HPT-JT syndrome and the relationship between the HRPT2 gene and parathyroid tumours were investigated. We report the identification of the HRPT2 gene, located on chromosome 1q, a gene encoding a protein referred to as parafibromin. Germ-line mutations in this gene are responsible for the HPT-JT syndrome and a part of the sporadic parathyroid carcinomas. Loss of parafibromin in immunohistochemical staining seems a promising marker in the diagnosis of parathyroid carcinomas. Furthermore, we tried to gain insight in the molecular mechanisms of parathyroid tumourigenesis to improve the accuracy of diagnosis of these tumours. Molecules such as APP, E-cadherin andCASR might play a role in HRPT2 driven tumourigenesis.