Endocrine Abstracts

Background: Pituitary adenomas are the most common intracranial neoplasm, with a slow-growing, locally invasive phenotype. Some result from syndromes or isolated germ-line mutations, while approximately 60% have no currently identified somatic mutation implicated in tumorigenesis. High throughput technologies such as microarray, RNA sequencing (RNAseq) and next-generation sequencing (NGS, incorporating whole genome- and exome sequencing) have recently been used to identify alt...

Objectives: Somatotropinomas form three subgroups with distinct methylation profiles1, one matching the sparsely granulated (SG) and the other two matching the densely granulated phenotypes (DG-A and DG-B). Publicly accessible raw methylation data1 and our RNA microarray data were analysed to identify differentially methylated regions (DMRs) and enriched genes between SG, DG-A and DG-B and normal anterior pituitary gland (NP), genes showing differential m...

Background: Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) gene have been implicated in the tumorigenesis of patients with familial isolated pituitary adenoma (FIPA). Around 25% of FIPA patients have an identified AIP mutation; in the remainder of FIPA patients, molecular mechanisms involved in pituitary tumorigenesis have yet to be elucidated.Aims: To identify the genes and molecular mechanisms involved i...

Background: Olfactory neuroblastoma (ONB), a neuroendocrine nasal tumour, exhibits a range of phenotypes from indolent to very aggressive. Even early disease is associated with high (60%) recurrence rates, while advanced disease has 1.5y disease-free and 2.5y overall mean survival. Medical treatments against primary and recurrent disease as well as prognostic biomarkers are urgently required. The few studies available suggest that mTOR/MAPK and Sonic Hedgehog signalling has a ...

Background: Germline mutations of the AIP tumour suppressor gene are associated with familial and sporadic pituitary adenomas, yet the tumorigenic mechanisms remain unclear. In addition, AIP protein expression in somatotroph adenomas from patients without AIP mutations correlates with clinical behaviour and somatostatin analogues responsiveness. Understanding the regulation of AIP gene expression will help uncover its pituitary tumour-suppressor role.Aim...

Background: Heterozygote mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.Aims: To investigate the tumour suppre...

Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations have been identified in ~15% of patients with familial isolated pituitary adenomas (FIPA). In addition, dysregulation of the cyclic adenosine monophosphate (cAMP) signalling pathway has been identified in both syndromic and sporadic somatotropinomas. While crosstalk between these two systems is known to occur, the exact mechanism of interaction remains elusive. The identification of direct binding...

Introduction: Pseudoacromegaly encompasses a group of conditions in which patients have clinical features of acromegaly or gigantism, but no GH or IGF-1 excess. With systematically reviewing all published cases (n=76) of patients with pseudoacromegaly who were evaluated due to a clinical suspicion of acromegaly, we identified key distinguishing features which need to be recognized.Materials and Methods: A systematic search using the terms pseudo...

Introduction: Aryl hydrocarbon receptor interacting protein (AIP) is a multifunctional co-chaperone protein: it behaves as a tumour suppressor in the pituitary, but may have other roles including oncogenic function in other tissues. Protein phosphorylation is an important posttranslational modification that regulates protein activity, which is crucial for understanding protein function. To understand the molecular pathways altered in AIP deficient cells, we have performed glob...

Objectives: Somatotropinomas can be divided into three subgroups based on their distinct DNA methylation profiles1, one matching sparsely granulated (SG) and the other two matching densely granulated phenotypes (DG-A and DG-B). Sparsely granulated adenomas show fibrous body formation on cytokeratin immunohistochemistry, compared to diffuse staining in densely granulated adenomas. Methylation1 and gene expression data were analysed to identify (i) differen...