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

Background Recently, germ-line 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 analyzed somatic mutations in 40 tumours. Second, DNA from corresponding leukocytes was analyzed in tumours showing genetic changes of the AIP gene. Results Germ-line mutation of AIP was found in an IFS family. Biallelic inactivation of AIP by a combination of germ-line mutation and loss of heterozygosity was 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 germ-line 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 germ-line 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