Endocrine Abstracts

Introduction: Germline mutations in succinate dehydrogenase complex (SDHx) are a risk factor for developing Pheochromocytoma (Pheo) and/or Paragangliomas (PGL) (named together PPGL), being responsible for approximately 30% of cases. The precise genotype-phenotype correlations and best management strategies are still uncertain.Objective: To characterize the clinical features and genotype-phenotype associations in a group of SDHx-mutated PPGL patients....

The unresponsiveness of anaplastic thyroid carcinomas (ATCs) to multimodal therapy represents the major challenge in thyroid cancer treatment. Our group previously showed that genes involved in cell cycle are differentially expressed in ATCs compared to normal thyroid, and that the most common mutations found in these tumours are related with proliferation and cell cycle genes, namely TP53, RAS, CDKN2A and CDKN2B. Therefore, these genes are ...

Background: Germline heterozygous mutations in the MEN1 gene located on chromosome 11q13, predisposes to the development of tumors in multiple endocrine tissues. The MEN1 gene encodes a protein of 610 amino acid residues, known as menin which is involved in genome stabilization as well as in several steps of cellular division, conferring tumor suppression activity in MEN1-associated target tissues. The three main endocrine tissues affected by tumors in MEN1 are parathyroid (95...

Introduction: Familial hypocalciuric hypercalcaemia (FHH) is a rare genetically heterogeneous disorder, with 3 variants described. An inactivating mutation in the calcium sensor receptor (CASR) gene causes the subtype 1, which represents 65% of the cases.It is charaterised by hypercalcaemia and hypocalciuria with normal or elevated PTH. FHH is generally assymptomatic and treatment is not needed. Differential diagnosis with primary hyperparathyroidism (PH...

Introduction and objectives: Anaplastic thyroid cancer (ATC) has a very low overall survival (OS) and progression free survival (PFS) due to fast growth and resistance to non-target therapies. A recent phase II study showed a dramatic increase in OS and PFS of BRAF V600E mutated ATC patients treated with Dabrafenib and Trametinib (DT). However as commonly reported in melanoma durable responses in ATC may be compromised by resistance mechanisms. Until now only a few ca...

Introduction and objectives: The cyclin-dependent kinases CDK4 and CDK6 are key regulators of the cell cycle entry, by phosphorylating the onco-suppressor retinoblastoma protein (pRb). CDK4/6 inhibitors (CDK4i) are already established as standard first-line treatment against advanced Estrogen Receptor-positive breast tumors, and have emerged as novel drugs to treat various pRb-proficient chemotherapy-resistant cancers. Presence of activating T172-phosphorylation of CDK4 in bre...

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers.Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTC).<p class="abstext"...