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: 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...

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...

Introduction: Somatotroph adenomas are GH producing pituitary adenomas. There are two main types based on granulation pattern: sparsely and densely granulated. Each type also has their own fibrous body pattern. Sparsely granulated (SG) have a ‘dot-like’ fibrous body pattern and the densely granulated (DG) have a ‘perinuclear’ fibrous body pattern. The fibrous bodies are mainly composed of keratin 8. Previous microarray analysis revealed six differentially e...

Background: Familial isolated pituitary adenoma (FIPA) is recently identified autosomal dominant condition with incomplete penetrance. Heterozygote mutations have been identified in the aryl-hydrocarbon receptor interacting protein (AIP) gene in 20–30% of FIPA families. AIP mutation positive patients have distinct phenotype: the disease is occurring at a younger age and have more aggressive tumours.Aims: The aim of this study was to perform comparat...

Background: Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with incomplete penetrance. Heterozygote mutations have been identified in the aryl-hydrocarbon receptor interacting protein (AIP) gene in 20% of FIPA families causing young-onset aggressive tumours.Aims: The aim of this study was to perform comparative gene expression microarray analysis of familial AIP positive and AIP negative adenomas and compare them to sporadi...

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...