Identification of novel genetic variants in phosphodiesterase 8B (PDE8B), a cAMP-specific phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumours

• Published in: Clinical endocrinology (Oxford) 2012-08, Vol.77 (2), p.195-199
• Main Authors: Rothenbuhler, Anya, Horvath, Anelia, Libé, Rossella, Faucz, Fabio R., Fratticci, Amato, Raffin Sanson, Marie L., Vezzosi, Delphine, Azevedo, Monalisa, Levy, Isaak, Almeida, Madson Q., Lodish, Maya, Nesterova, Maria, Bertherat, Jérôme, Stratakis, Constantine A.
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - genetics; Adrenal Cortex - metabolism; Adrenal Gland Neoplasms - genetics; Adrenal glands; Biological and medical sciences; Case-Control Studies; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetic Predisposition to Disease; Genetic Variation - genetics; Humans; Male; Medical research; Medical sciences; Miscellaneous; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2012.04366.x

Summary Background Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions. Objective To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours. Design and subjects This is a case–control study followed by functional analyses. Two hundred and sixteen unrelated patients with different types of adrenocortical tumours and 192 healthy control individuals participated in the study. Methods Bidirectional Sanger sequencing, in vitro cell line transfection and in silico modelling are used in this study. Results Nine different PDE8B sequence changes, six novel and three previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico. Conclusion PDE8B is another PDE gene in which variations may contribute to predisposition of adrenocortical tumours.