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.
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.
Authors: Anelia Horvath; Christoforos Giatzakis; Audrey Robinson-White; Sosipatros Boikos; Elizabeth Levine; Kurt Griffin; Erica Stein; Virginia Kamvissi; Payal Soni; Ioannis Bossis; Wouter de Herder; J Aidan Carney; Jérôme Bertherat; Peter K Gregersen; Elaine F Remmers; Constantine A Stratakis Journal: Cancer Res Date: 2006-12-15 Impact factor: 12.701
Authors: L S Kirschner; J A Carney; S D Pack; S E Taymans; C Giatzakis; Y S Cho; Y S Cho-Chung; C A Stratakis Journal: Nat Genet Date: 2000-09 Impact factor: 38.330
Authors: C Gicquel; M Leblond-Francillard; X Bertagna; A Louvel; Y Chapuis; J P Luton; F Girard; Y Le Bouc Journal: Clin Endocrinol (Oxf) Date: 1994-04 Impact factor: 3.478
Authors: F Beuschlein; M Reincke; M Karl; W D Travis; C Jaursch-Hancke; S Abdelhamid; G P Chrousos; B Allolio Journal: Cancer Res Date: 1994-09-15 Impact factor: 12.701
Authors: Donald H Maurice; Hengming Ke; Faiyaz Ahmad; Yousheng Wang; Jay Chung; Vincent C Manganiello Journal: Nat Rev Drug Discov Date: 2014-04 Impact factor: 84.694
Authors: Rodrigo B de Alexandre; Anelia D Horvath; Eva Szarek; Allison D Manning; Leticia F Leal; Fabio Kardauke; Jonathan A Epstein; Dirce M Carraro; Fernando A Soares; Tatiyana V Apanasovich; Constantine A Stratakis; Fabio R Faucz Journal: Endocr Relat Cancer Date: 2015-05-15 Impact factor: 5.678
Authors: Fady Hannah-Shmouni; Andreas G Moraitis; Vladimir Valera Romero; Fabio R Faucz; Spyridon A Mastroyannis; Annabel Berthon; Richard A Failor; Maria Merino; Andrew P Demidowich; Constantine A Stratakis Journal: Horm Metab Res Date: 2017-11-28 Impact factor: 2.936
Authors: Crystal D C Kamilaris; Fady Hannah-Shmouni; Constantine A Stratakis Journal: Best Pract Res Clin Endocrinol Metab Date: 2020-05-23 Impact factor: 4.690