Screening of <i>AIP</i> Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas

Tuncer, Feyza Nur; Dogansen, Sema Ciftci; Serbest, Esin; Tanrikulu, Seher; Ekici, Yeliz; Bılgıç, Bilge; Yarman, Sema

doi:10.1089/gtmb.2018.0133

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Given the low prevalence of germline mutations within studies including patients with sporadic PA (11,27,29,31,50,51,52), the need for genetic screening in young patients is questionable. In our cohort, prolactinomas were greatly represented (44.7%) and despite identifying AIP and MEN1 gene mutations in these types of tumours, they did not lead to a more severe phenotype compared to the general population of PA.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Piscina

Najera

Rica

et al. 2021

European Journal of Endocrinology

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Objective: Pituitary adenomas (PA) are rare in young patients and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients. Design: Clinical and molecular analysis of 235 patients (age ≤30 years) with a PA. Clinicians from several Spanish and Chilean hospitals provided data. Methods: Genetic screening was performed via next-generation sequencing and comparative genomic hybridization array. Clinical variables were compared among paediatric, adolescent (<19 years) and young adults’ (≥19-30 years) cohorts and types of adenomas. Phenotype-genotype associations were examined. Results: Among the total cohort mean age was 17.3 years. Local mass effect symptoms were present in 22.0% and prolactinomas were the most frequent (44.7%). Disease-causing germline variants were identified in 22 individuals (9.3%), more exactly in 13.1% and 4.7% of the populations aged 0-19 and 19-30 years, respectively; genetically positive patients were younger at diagnosis and had larger tumour size. Healthy family carriers were also identified. Conclusions: Variants in genes associated with syndromic forms of PAs were detected in a large cohort of apparently sporadic pituitary tumours. We have identified novel variants in well-known genes and set the possibility of incomplete disease penetrance in carriers of MEN1 alterations or a limited clinical expression of the syndrome. Despite the low penetrance observed, screening of AIP and MEN1 variants in young patients and relatives is of clinical value.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Piscina

Najera

Rica

et al. 2021

European Journal of Endocrinology

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“…In the FIPA setting, AIP pathogenic variants are demonstrated in about 20% of families, while in cohorts of unselected apparently sporadic pituitary adenomas AIP pathogenic variants are rarely found -in less than 4% (11,84). However, in young adults (diagnosed < 30 years of age) with apparently sporadic adenomas (mostly macroadenomas), the prevalence of AIP pathogenic variants was higher, ranging between 1.6 and 13% (85,86,87,88,89,90,91,92,93). Further decreasing the age of diagnosis (pediatric/ adolescent patients <18 year/old) increases the frequency of AIP pathogenic variants to 11-25% (85,87,94,95,96,97,98).…”

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 99%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.

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“…Numerous screening studies in series of patients with unselected pituitary adenomas, pediatric-onset pituitary adenomas, pituitary macroadenomas, and FIPA have been performed (13,15,17,28,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). About two-thirds of individuals with AIPvar-related pituitary adenomas present with acromegaly, usually in the setting of FIPA, and among this group, pituitary gigantism occurs in 32% (16).…”

Section: Discussionmentioning

confidence: 99%

The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene

Vroonen,

Beckers,

Camby

et al. 2023

Front. Endocrinol.

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IntroductionProlactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar).MethodsWe compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (“unselected”, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).ResultsAIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups.DiscussionAIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.

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Screening of AIP Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas

Cited by 8 publications

References 42 publications

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Somatic and germline mutations in the pathogenesis of pituitary adenomas

The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene

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