‘At the very same time there was published a study carried out by Finnish researches. It described a new gene with a predisposition to pituitary adenoma: the AIP, Aryl Hydrocarbon Receptor-Interacting Protein’, explains the scientist. ‘They had brought to light mutations of this gene in certain families of which certain members were affected by acromegaly and prolactinoma,’ he continues. Without delaying Albert Beckers thus decided to study if mutations of this gene were also found in the members of families subject to FIPA. The conclusion: ‘We found mutations of the AIP gene in 15% of the patients and we discovered 9 new mutations of this gene,’ reveals Albert Beckers. The scientific article related to this work, published in the JCEM (4), earned Albert Beckers and his colleagues the prize for the best Belgian article on internal medicine in 2007.

Susceptibility genes in the line of fire

Since these discoveries Albert Beckers’ team has continued its research into pituitary adenoma and is constantly extending knowledge about these pathologies. The Head of the Liège CHU Department of Endocrinology has just published the results of an international study he has directed (5). This study looks into the clinical characteristics of pituitary adenoma in people who have a mutated version of the AIP gene. ‘They are different to the clinical characteristics of the adenoma which appear during a type 1 multiple endocrine neoplasia because the patients are more frequently affected by acromegaly and gigantism and much less by prolactinoma,’ specifies Albert Beckers. In addition, in comparing patients affected by pituitary adenoma who have a mutation at the level of the AIP gene to those who do not have such a mutation the endocrinologist noticed that the former were younger at the moment the disease was diagnosed (around 20 years instead of 40 years), that the diameter of their tumour was larger and that they responded less well to treatment. ‘Similarly, if we look at particularly aggressive pituitary adenoma we can see that the frequency of AIP gene mutations in patients affected by it is greater,’ continues the Professor.

Currently on the track of genes with a predisposition to pituitary adenoma, Albert Beckers is working jointly with Professor Michel Georges, who directs the ULg’s Unit of Animal Genomics. ‘We are working with patients from a family which does not have AIP gene mutations in the hope of discovering another gene with a predisposition to pituitary adenoma in this particular family,’ points out Albert Beckers. To do so the scientists first of all located the predisposition regions and are now carrying out complete genome sequencing of the family members and are comparing these genomes. ‘It is necessary to detect the regions common to the patients affected. In this case we are talking of about 120 candidate genes.’ There thus remains a sizeable list of genes to be ‘tested’ in order to put the finger on the one or more genes involved in the appearance of pituitary adenoma. At the present time new genome sequencing studies are under way. Albert Beckers and his team have already been able to eliminate certain of these candidate genes and are on a promising path towards discovering a new gene with a predisposition to these tumours.

(4) A.F. Daly, J-F Vanbellinghen, S.K. Khoo, M-L. Jaffrain-Rea, L. Naves, M.A. Guitelman, A. Murat, P.   Emy, A-P.Gimenez-Roqueplo, G. Tamburrano, G. Raverot, A. Barlier, W. de Herder, A. Penfornis, E. Ciccarelli, B. Estour, P. Lecomte, B. Gatta, O. Chabre, M-I. Sabate, X. Bertagna, N. Garcia Basavilbaso, G. Stalldecker, A. Colao, P. Ferolla, H-L. Wemeau, P. Caron, J-L. Sadoul, A. Oneto, F. Archambaud, A. Calender, O. Sinilnikova, C. Montanana, F. Cavagnini, V. Hana, A. Solano, D. Delettieres, D.C. Luccio-Camelo, A. Basso, V. Rohmer, T. Brue, V. Bours, B. Tean Teh and A. Beckers. Aryl Hydrocarbon Receptor Interacting Protein Gene Mutations in Familial Isolated. Pituitary Adenomas : Analysis in 73 families. J. Clin. Endocrinol. Metab, 92(5):1891-1896, 2007. Doi : 10.1210/ jc.2006-2513.  
(5) Adrian F. Daly1, Maria A. Tichomirowa1, Patrick Petrossians1, Elina Heliövaara, Marie-Lise Jaffrain-Rea, Anne Barlier, Luciana A. Naves, Tapani Ebeling, Auli Karhu, Antti Raappana, Laure Cazabat, Ernesto De Menis, Carmen Fajardo Montañana, Gerald Raverot, Robert J. Weil, Timo Sane, Dominique Maiter, Sebastian Neggers, Maria Yaneva, Antoine Tabarin, Elisa Verrua, Eija Eloranta, Arnaud Murat, Outi Vierimaa, Pasi I. Salmela, Philippe Emy, Rodrigo A. Toledo, Maria Isabel Sabaté, Chiara Villa, Marc Popelier, Roberto Salvatori, Juliet Jennings, Ángel Ferrandez Longás, José Ignacio Labarta Aizpún, Marianthi Georgitsi, Ralf Paschke, Cristina Ronchi, Matti Valimaki, Carola Saloranta, Wouter De Herder, Renato Cozzi, Mirtha Guitelman, Flavia Magri, Maria Stefania Lagonigro, Georges Halaby, Vinciane Corman, Marie-Thérèse Hagelstein, Jean-François Vanbellinghen, Gustavo Barcelos Barra, Anne-Paule Gimenez-Roqueplo, Fergus J. Cameron, Françoise Borson-Chazot, Ian Holdaway, Sergio P. A. Toledo, Günter K. Stalla, Anna Spada, Sabina Zacharieva, Jerome Bertherat, Thierry Brue, Vincent Bours, Philippe Chanson, Lauri A. Aaltonen and Albert Beckers. Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study. The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 11 E373-E383.