The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas

Summary 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.