<i>Aryl hydrocarbon receptor interacting protein</i> (<i>AIP</i>) gene mutation analysis in children and adolescents with sporadic pituitary adenomas

Georgitsi, Marianthi; Menis, Ernesto De; Cannavò, Salvatore; Mäkinen, Markus J.; Tuppurainen, Karoliina; Pauletto, Paolo; Curtò, Lorenzo; Weil, Robert J.; Paschke, Ralf; Zieliński, Grzegorz; Wasik, A.; Lubiński, Jan; Vahteristo, Pia; Karhu, Auli; Aaltonen, Lauri A.

doi:10.1111/j.1365-2265.2008.03266.x

Cited by 74 publications

(38 citation statements)

References 42 publications

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“…near 7% (7,8). This prevalence reaches 14.3% in patients with GH-secreting tumors diagnosed before 25 years old (28). All these data lead us to propose to limit the genetic screening to subjects younger than 30 years old (Fig.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Cuny

Pertuit

Sahnoun-Fathallah

et al. 2013

European Journal of Endocrinology

146

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Context: Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) have been identified in young patients (age %30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of multiple endocrine neoplasia type 1 (MEN1) mutations in such a population. Objective: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age %30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. Design: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. Patients and settings: One hundred and seventy-four patients from endocrinology departments of 15 French University Hospital Centers were eligible for this study. Results: Twenty-one out of 174 (12%) patients had AIP (nZ15, 8.6%) or MEN1 (nZ6, 3.4%) mutations. In pediatric patients (age %18 years old), AIP/MEN1 mutation frequency reached nearly 22% (nZ10/46). AIPmut and MEN1mut were identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients respectively; they each accounted for 4/74 (5.4%) prolactinoma (PRL) patients with mutations. Half of those patients (nZ3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the eight corticotroph adenomas or the single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. Conclusion: Mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly PRL, and together with AIP, we suggest genetic analysis of MEN1 in such a population.

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Section: Discussionmentioning

confidence: 99%

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Cuny

Pertuit

Sahnoun-Fathallah

et al. 2013

European Journal of Endocrinology

146

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“…By contrast, germline AIP mutations have rarely been encountered in unselected patients with sporadic PA (<1%) [16]. One exception of great interest is that AIP mut may appear more frequently in young patients with growth hormone (GH)-or prolactin-secreting macroadenomas [17][18][19]. According to preliminary data from international series, distinct changes in the germline AIP sequence can be observed in up to 16% of young patients with pituitary macroadenomas [20].…”

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confidence: 99%

Pituitary adenomas in young patients: when should we consider a genetic predisposition?

Jaffrain-Rea

Tichomirowa

Daly

et al. 2009

Expert Review of Endocrinology & Metabolism

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“…As such, the clinical application of IHC for AIP as a screening tool remains controversial. Germline AIP mutations are very rare in patients with sporadic PA, although they can be encountered in young acromegalics (Barlier et al 2007, Iwata et al 2007, Georgitsi et al 2008a). In addition, although variations in AIP expression among sporadic PA have been recently reported according to their functional phenotype (Leontiou et al 2008), their potential relationship with tumour-evolutive features has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications

Jaffrain-Rea¹,

Angelini

Gargano

et al. 2009

Endocrine-Related Cancer

133

103

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3Fondazione 'Carlo Ferri' per la prevenzione e la cura dei tumori, via Edmondo Riva 42, 00015 Monterotondo, Italy AbstractGermline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (nZ103), including 17 with AIP mutations (AIP mut ). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P!0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (PZ0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (PZ0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP mut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

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Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas

Cited by 74 publications

References 42 publications

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Pituitary adenomas in young patients: when should we consider a genetic predisposition?

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications

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