BACKGROUND: Recently, germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene located on 11q13 were identified in patients with pituitary adenoma predisposition. AIM/PATIENTS AND METHODS: We investigated the involvement of the AIP gene in one family with isolated familial somatotropinomas (IFS). To investigate the role of AIP in sporadic GH-secreting adenomas, we first analysed somatic mutations in 40 tumours. Second, DNA from corresponding leucocytes was analysed in tumours showing genetic changes of the AIP gene. RESULTS: Germline mutation of AIP was found in an IFS family. Bi-allelic inactivation of AIP by a combination of germline mutation and loss of heterozygosity were confirmed in two pituitary adenomas. Mutation analysis of the AIP gene in the 40 sporadic GH-secreting adenomas showed no mutations except for a missense mutation, suggesting that germline mutations in patients diagnosed with sporadic acromegaly or gigantism were rare. In a patient with gigantism, a missense mutation of V49M was identified at the germline level. CONCLUSION: Based on these results, we conclude that the loss of function of AIP contributes to IFS, but not for most Japanese sporadic GH-secreting adenomas.
BACKGROUND: Recently, germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene located on 11q13 were identified in patients with pituitary adenoma predisposition. AIM/PATIENTS AND METHODS: We investigated the involvement of the AIP gene in one family with isolated familial somatotropinomas (IFS). To investigate the role of AIP in sporadic GH-secreting adenomas, we first analysed somatic mutations in 40 tumours. Second, DNA from corresponding leucocytes was analysed in tumours showing genetic changes of the AIP gene. RESULTS: Germline mutation of AIP was found in an IFS family. Bi-allelic inactivation of AIP by a combination of germline mutation and loss of heterozygosity were confirmed in two pituitary adenomas. Mutation analysis of the AIP gene in the 40 sporadic GH-secreting adenomas showed no mutations except for a missense mutation, suggesting that germline mutations in patients diagnosed with sporadic acromegaly or gigantism were rare. In a patient with gigantism, a missense mutation of V49M was identified at the germline level. CONCLUSION: Based on these results, we conclude that the loss of function of AIP contributes to IFS, but not for most Japanese sporadic GH-secreting adenomas.
Authors: Rodrigo A Toledo; Berenice B Mendonca; Maria Candida B V Fragoso; Iberê C Soares; Madson Q Almeida; Michelle B Moraes; Delmar M Lourenço; Venâncio A F Alves; Marcello D Bronstein; Sergio P A Toledo Journal: Clinics (Sao Paulo) Date: 2010-04 Impact factor: 2.365