Absence of germline AIP mutations in early onset sporadic somatotropinomas

Leonor Gomes; Hugo Prazeres; Isabel Paiva; Cristina Ribeiro; Olinda Rebelo; Teresa Martins; Manuela Lacerda; Manuela Carvalheiro

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Endocrine Abstracts (2007) 14 OC4.3

ECE2007 Oral Communications Neuroendocriology basis (7 abstracts)

Absence of germline AIP mutations in early onset sporadic somatotropinomas

Leonor Gomes ¹ , Hugo Prazeres ² , Isabel Paiva ¹ , Cristina Ribeiro ¹ , Olinda Rebelo ³ , Teresa Martins ² , Manuela Lacerda ² & Manuela Carvalheiro ¹

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¹Serviço de Endocrinologia, Diabetes e Metabolismo dos Hospitais da Universidade de Coimbra, Coimbra, Portugal; ²Laboratório de Patologia Molecular do Serviço de Anatomia Patológica do Centro Regional de Oncologia de Coimbra do Instituto Português de Oncologia, EPE, Coimbra, Portugal; ³Serviço de Anatomia Patológica dos Hospitais da Universidade de Coimbra, Coimbra, Portugal.

Objective: The pathogenesis of pituitary tumours is still incompletely understood. Somatotropinomas occur both sporadically and in the context of familial syndromes, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC) and isolated familial somatotropinoma (IFS). Recently, germline mutations were reported in AIP (aryl hydrocarbon receptor interacting protein) gene in Finish and Italian families and in Finish patients with apparently sporadic pituitary tumours. The aim of this study was to determine if AIP gene mutations influence individual susceptibility to develop sporadic pituitary somatotropinomas in a group of young patients originating from the central region of Portugal.

Methods: Blood samples were obtained from 20 patients (8 males and 12 females) with sporadic somatotrophinomas, including 6 plurihormonal for GH and PRL, who were diagnosed when they were younger than 35 years of age (mean age 25.7±4.97, 16-33 years). Detection of the AIP germline mutations was carried out by PCR amplification of genomic DNA, followed by direct sequencing of the entire gene coding sequence and intron-exon boundaries as previously described.

Results: In this series of patients, with early onset sporadic oversecreting-GH pituitary adenomas, no AIP germline mutations were found. A heterozygous synonymous C→T polymorphism (Asp45Asp) was found in a single patient.

Conclusions: Our results provide evidence that AIP germline mutations are not associated with sporadic pituitary tumours. We studied patients diagnosed at young ages, with a hypothetically higher probability of harbouring occult germline mutations. The absence of germline mutations in this group of patients suggests that AIP germline mutations probably do not play an important role in the pathogenesis of sporadic pituitary somatotropinomas. Similar observations have been made by other groups. Further studies are needed in order to identify other genetic factors underlying early onset sporadic pituitary tumours.