scholarly journals SNPs in the aryl hydrocarbon receptor-interacting protein gene associated with sporadic non-functioning pituitary adenoma

2016 ◽  
Vol 11 (3) ◽  
pp. 1142-1146 ◽  
Author(s):  
YESHUAI HU ◽  
JUN YANG ◽  
YONGKAI CHANG ◽  
SHUNCHANG MA ◽  
JIANFA QI
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Protein Gene ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Familial isolated pituitary adenoma syndrome

2011 ◽  
Vol 152 (18) ◽  
pp. 722-730 ◽  
Author(s):  
Judit Dénes ◽  
Márta Korbonits ◽  
Erika Hubina ◽  
Gábor László Kovács ◽  
László Kovács ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Protein Gene ◽  
Gene Mutations ◽  
Carney Complex ◽  
Incomplete Penetrance ◽  
Causative Gene ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor. Orv. Hetil., 2011, 152, 722–730.

MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro

2012 ◽  
Vol 303 (6) ◽  
pp. E708-E719 ◽  
Author(s):  
Giampaolo Trivellin ◽  
Henriett Butz ◽  
Juliette Delhove ◽  
Susana Igreja ◽  
Harvinder S. Chahal ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Tumor Suppressor ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Expression Profiles ◽  
Luciferase Assay ◽  
Human Neuroblastoma ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Abnormal microRNA (miRNA) expression profiles have recently been associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation; miRNAs are small noncoding RNAs that inhibit posttranscriptional expression of target mRNAs by binding to target sequences usually located in the 3′-UTR. In this study, we investigated the role played by miR-107, a miRNA associated with different human cancers, in sporadic pituitary adenomas and its interaction with the pituitary tumor suppressor gene aryl hydrocarbon receptor-interacting protein ( AIP). miR-107 expression was evaluated in pituitary adenoma and normal pituitary samples using microRNA screen TLDA (TaqMan Low-Density Array) and RT-qPCR assays. We show that miR-107 expression was significantly upregulated in GH-secreting and nonfunctioning pituitary adenomas. We found that human AIP-3′-UTR is a target of miR-107 since miR-107 inhibited in vitro AIP expression to 53.9 ± 2% of the miRNA control in a luciferase assay and reduced endogenous AIP mRNA expression to 53 ± 22% of the miRNA control in human cells. However, we did not observe a negative correlation between AIP and miR-107 expression in the human tumor samples. Furthermore, we show that miR-107 overexpression inhibited cell proliferation in human neuroblastoma and rat pituitary adenoma cells. In conclusion, miR-107 is overexpressed in pituitary adenomas and may act as a tumor suppressor. We have identified and confirmed AIP as a miR-107 target gene. Expression data in human samples suggest that the expression of AIP and miR-107 could be influenced by a combination of tumorigenic factors as well as compensatory mechanisms stimulated by the tumorigenic process.

scholarly journals Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations

2013 ◽  
Vol 20 (5) ◽  
pp. 753-766 ◽  
Author(s):  
Marie-Lise Jaffrain-Rea ◽  
Sandra Rotondi ◽  
Annarita Turchi ◽  
Gianluca Occhi ◽  
Anne Barlier ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Primary Cultures ◽  
Gene Mutations ◽  
Somatostatin Analogues ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Tumour Shrinkage ◽  
Suprasellar Extension

Germline aryl hydrocarbon receptor interacting protein (AIP) gene mutations confer a predisposition to pituitary adenoma (PA), predominantly GH-secreting (GH-PA). As recent data suggest a role for AIP in the pathogenesis of sporadic GH-PA and their response to somatostatin analogues (SSA), the expression of AIP and its partner, aryl hydrocarbon receptor (AHR), was determined by semiquantitative immunohistochemistry scoring in 62 sporadic GH-PA (37 treated with SSA preoperatively). The influence ofGspstatus was studied in a subset of tumours (n=39, 14Gsp+) and six GH-PA were available for primary cultures. AIP and AHR were detected in most cases, with a positive correlation between AIP and cytoplasmic AHR (P=0.012). Low AIP expression was significantly more frequent in untreated vs SSA-treated tumours (44.0 vs 20.5%,P=0.016). AHR expression or localisation did not differ between the two groups. Similarly,in vitrooctreotide induced a median twofold increase in AIP expression (range 1.2–13.9,P=0.027) in GH-PA. In SSA-treated tumours, the AIP score was significantly higher in the presence of preoperative IGF1 decrease or tumour shrinkage (P=0.008 andP=0.014 respectively). In untreated tumours, low AIP expression was significantly associated with invasiveness (P=0.028) and suprasellar extension (P=0.019). The only effect ofGspstatus was a significantly lower nuclear AHR score inGsp+vsGsp−tumours (P=0.025), irrespective of SSA. In conclusion, AIP is involved in the aggressiveness of sporadic GH-PA, regardless ofGspstatus, and AIP up-regulation in SSA-treated tumours is associated with a better preoperative response, with no clear role for AHR.

Familial Isolated Pituitary Adenomas

2009 ◽  
Vol 05 (0) ◽  
pp. 55
Author(s):  
Harvinder S Chahal ◽  
VK Ajith Kumar ◽  
Márta Korbonits ◽  
◽  
◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Medical Therapy ◽  
Pituitary Adenomas ◽  
Protein Gene ◽  
Family Members ◽  
Interacting Protein ◽  
Genetic Characteristics ◽  
Aryl Hydrocarbon ◽  
Intense Research

Over the last century several families have been described with familial isolated pituitary adenomas (FIPAs). Most commonly, family members have acromegaly or prolactinoma, but other types of pituitary adenomas can also occur. Recently, mutations in theAIP(aryl hydrocarbon receptor interacting protein) gene have been found to occur in 30–50% of FIPA patients, while for the rest of the patients the gene causing the disease is currently unknown and is a topic of intense research. Tumours in patients withAIPmutations are diagnosed at significantly younger ages and tend to be larger. Often the response to medical therapy in these patients is poor. This article discusses the clinical and genetic characteristics of this relatively recently recognised disease.

scholarly journals Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas

2007 ◽  
Vol 157 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Laure Cazabat ◽  
Rossella Libè ◽  
Karine Perlemoine ◽  
Fernande René-Corail ◽  
Nelly Burnichon ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Protein Gene ◽  
Mutation Screening ◽  
Germline Mutations ◽  
Large Cohort ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Exon 4

Objective: Germline mutations of the aryl hydrocarbon receptor-interacting protein gene (AIP) have recently been described in three families with GH or prolactin-secreting tumors, as well as in a few patients with apparently sporadic somatotropinomas. The aim of the study was to determine the prevalence of AIP mutations in a large cohort of patients with apparently sporadic GH-secreting tumors. Design: One hundred and fifty-four patients were included in a prospective cohort designed to study the genetic predisposition to GH-secreting tumors together with 270 controls. Methods: In all these subjects, the entire coding sequence of the AIP gene was screened for germline mutations. Results: AIP mutations were detected in 5 out of 154 patients (3%): nonsense mutations in exon 4 (p.Lys201X; n = 2) and in exon 6 (p.Arg304X), one deletion in exon 3 (c.404delA; pHis135LeufsX21), and one mutation affecting the splice acceptor site of exon 4 (c.469-2 A > G). The five patients with an AIP mutation were significantly younger (mean age ± S.D.: 25 ± 10 vs 43 ± 14 years, P = 0.005) and three of them presented with gigantism. One missense mutation (p.Arg304Gln) was found in a single patient that was absent in all controls. Conclusions: Germline mutations of the AIP gene were found in a small proportion of patients with sporadic pituitary somatotropinomas. This study shows that age and gigantism are simple clinical features which can help to select patients for mutation screening. It also supports the role of AIP in pituitary tumorigenesis.

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