Searchable abstracts of presentations at key conferences in endocrinology

ea0032s31.1 | Clinical impact of rare mutations in endocrinology | ECE2013

Does a new mutation always predict a new disease? Lessons from p27 mutations

Pellegata Natalia

A few years ago a novel multiple endocrine neoplasia syndrome, named MEN type 4 (MEN4), was discovered thanks to studies conducted on a MEN syndrome in the rat (named MENX). Rat and human syndromes are both caused by germline mutations in the Cdkn1b/CDKN1B gene encoding p27Kip1, a putative tumor suppressor which binds to and inhibits cyclin/cyclin dependent kinase complexes, thereby inhibiting cell cycle progression. MEN4 patients carry heterozygous mutations...

ea0026s3.3 | Molecular mechanisms in neuroendocrine tumours | ECE2011

Lessons from MENX

Pellegata Natalia

MENX is a recently identified multiple endocrine neoplasia (MEN) syndrome in the rat. Affected animals develop multiple neuroendocrine tumors (NETs) with high penetrance and at young age, specifically: bilateral pheochromocytoma (100%), multifocal pituitary adenoma (100%), multifocal thyroid C-cell hyperplasia, parathyroid hyperplasia, extra-adrenal pheochromocytoma (paragangliomas) and pancreatic islet cell hyperplasia. MENX is caused by a germline frameshift mutation of the ...

ea0049ep926 | Pituitary - Basic | ECE2017

Angiogenesis-related proteins in pituitary adenomas

Karabid Ninelia Minaskan , Atkinson Michael , Pellegata Natalia

Pituitary adenomas are frequent intracranial tumors that often associate with the hypersecretion of pituitary hormones or may be non-secreting (nonfunctioning pituitary adenomas, NFPA). Tumors resembling human NFPAs develop with complete penetrance in rats affected by the multiple endocrine neoplasia syndrome, MENX. This syndrome is caused by a germline loss of function mutation in p27Kip1. Gene expression array analysis performed in our group identified a considera...

ea0041ep592 | Endocrine tumours and neoplasia | ECE2016

Bone morphogenetic protein signaling as novel therapeutic target in pheochromocytoma

Richter Andrea , Leinhauser Ines , Pellegata Natalia

Introduction: Rats affected by the MENX syndrome develop bilateral pheochromocytoma (PCC) with complete penetrance. Transcriptome profiling of rat PCC identified Bmp7 (bone morphogenetic protein 7) as highly expressed in the tumors. Interestingly, 72% of human PCCs also showed elevated BMP7 expression. BMP7 plays pro- or anti-oncogenic roles in cancer in a cell type-dependent manner. To address the role of Bmp7 in PCC, its level was modulated in PCC cell line...

ea0037oc1.5 | Adrenal 1 | ECE2015

Norepinephrine transporter as a predictive marker of response to PI3K/mTOR inhibition in phaeochromocytoma

Lee Misu , Laitinen Iina , Braren Rickmer , Pellegata Natalia S

Currently, no effective medical therapy exists for inoperable phaeochromocytomas (PCCs). Thus, we investigated the antitumor potential of the dual PI3K/mTOR inhibitor NVP-BEZ235 against PCC in vivo. We employed a spontaneous model of endogenous aggressive PCCs (MENX rats), which closely recapitulate the human tumours. Administration of NVP-BEZ235 to MENX rats for 14 days inhibited proliferation (assessed by Ki67, NuSAP staining), vascularity (CD31, VEGFA), and induced...

ea0037gp.19.04 | Pituitary–Acromegaly | ECE2015

Molecular and pathological determinants of somatostatin analogue resistance: somatotropinomas in AIP mutated and X-LAG syndrome patients

Lee Misu , Daly Adrian , Rostomyan Liliya , Pellegata Natalia , Beckers Albert

Poor hormonal and tumour responses to somatostatin analogues (SSA) in acromegaly can occur although the aetiology is often unclear. Two genetic syndromes are associated with relative SSA resistance: acromegaly due to AIP mutations (AIPmut) and the newly described X-linked acrogigantism (X-LAG) syndrome due to chromosome Xq26.3 microduplications. We studied whether SSA resistance in these conditions was related to somatostatin receptor (SSTR) levels in tumour tissues. We studie...

ea0037ep702 | Pituitary: basic and neuroendocrinology | ECE2015

Molecular analysis of miRNA expression profiles in AIP mutation positive somatotropinomas

Falk Nikolai , Daly Adrian , Beckers Albert , Pellegata Natalia

Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) predispose to pituitary adenomas in young patients, often presenting as familial isolated pituitary adenoma (FIPA) kindreds. Pituitary adenomas in patients with AIP mutations (AIPmut) are usually somatotropinomas, which are more aggressive and have poorer responses to somatostatin analogues than their non-mutated counterparts. Given the rarity of this condition, the molecular pathogenesis of the...

ea0022p388 | Endocrine tumours &amp; neoplasia (<emphasis role="italic">Generously supported by Novartis</emphasis>) | ECE2010

Human presentation of MEN X syndrome

Maere Caroline , Pellegata Natalia , Praet Marleen , Giri Mimi , T'Sjoen Guy

Different multiple endocrine neoplasia (MEN) syndromes have been described in humans. These conditions are characterised by different combinations of multiple endocrine tumors based on specific genetic mutations, mainly the MEN1 gene (MEN type 1 syndrome) or in the RET proto-oncogene (MEN type 2). A syndrome encompassing components of both MEN type 1 and type 2, but which is caused by a mutation in the Cdkn1b gene encoding p27, has been described in rats, the so-called MEN X s...

ea0063gp5 | Adrenal and Neuroendocrine - Tumour | ECE2019

Pheochromocytoma’s of MENX rats belong to the pseudo-hypoxia cluster

Mohr Hermine , Gulde Sebastian , de Martino Daniela , Richter Susan , Pellegata Natalia

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells of the adrenal medulla and paraganglia of the autonomic nervous system, respectively. Despite a common origin, these tumors are quite heterogeneous in terms of driver mutations, copy number alterations and activated downstream-signaling pathways. Genome wide expression analysis has identified at least three main tumor clusters: a pseudo-hypoxic cluster, one with activation ...

ea0049oc8.1 | Neuroendocrinology | ECE2017

Elucidating the molecular mechanisms underlying AIP dependent tumorigenesis

Bogner Eva-Maria , Daly Adrian F. , Beckers Albert , Atkinson Michael J. , Pellegata Natalia S.

Pituitary adenomas (PAs) are benign neoplasms that comprise 10–20% of all intracranial tumors. Mutations in the aryl hydrocarbon receptor interacting protein (AIP) have been identified to cause a small subset of hereditary PAs. To study the mechanisms of tumor formation in patients with AIP-mutated PAs we conducted a miRNA array analysis comparing AIP-mutated PAs with AIP-wild type PAs. We found a novel and specific set of miRNAs differentially expressed between the two g...