Endocrine Abstracts

Objective: Currently, data about the molecular profile of multifocal papillary thyroid cancer (PTC) are still controversial. The aim of this study was to fully characterize by NGS the molecular profile of different histological variants in patients affected by multifocal PTCs.Methods: for this purpose, 12 multifocal PTC patients have been studied based to the following inclusion criteria: 1) a minimum of two tumors foci per patient with at least two diff...

Objectives: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate ...

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

Pheochromocytoma and paraganglioma (PPGL) are rare tumours, whose genetic profile has gained complexity over the last two decades. The list of genes involved in the development of this disease has been steadily growing, and there are currently more than 20 driver genes capable of explaining either the hereditary or sporadic nature of the disease. Although genetic diagnosis is achieved in about 75-80% of cases, the genetic aetiology remains to be explained not only in patients ...

The gastric mucosa is a dynamic and regenerative tissue that functions in extreme conditions of low pH, mechanical insults and bacterial exposure. The mucosa is composed of pit and neck cells which secrete protective mucus, parietal and chief cells that secrete acid and digestive enzymes, enteroendocrine cells that affect motility, secretion and satiety, rare tuft cells, and at two stem-cell compartments. We studied the response of the gastric mucosa to sleeve gastrectomy surg...

Inhibins and activins were discovered based on their abilities to inhibit and stimulate follicle-stimulating hormone (FSH) secretion from pituitary gonadotrope cells. These ligands are members of the TGFbeta superfamily of secreted ligands. Current dogma suggests that activin B produced by gonadotropes stimulates FSH production in an autocrine/paracrine manner. Inhibins A and B from the gonads suppress FSH by competing for binding to activin receptors. This binding is aided by...

The advent of new genetic techniques that allow for high-throughput sequencing in surgical tumour tissues and germline DNA has boosted progress in many fields of biomedical research. The technique has been proven to be particularly fruitful in the area of endocrine tumours with many new driver genes being identified over the last few years that are involved in cell growth but more importantly in hormonal autonomy. For the adrenal gland examples account for aldosterone and cort...

During the last two decades the Scientific Community has assisted to an exponential increase of knowledge of genetic factors related to cancer susceptibility, as well as of key molecular mechanisms involved in tumour progression. In part, this has been the result of using high-throughput platforms able to interrogate any part of the genome following a hypothesis-free strategy. Without a doubt, the success achieved in recent years has to do not only with the improvement in the ...

Epigenetic reprogramming including altered transcription factor binding and altered patterns of chromatin and DNA modifications are now accepted as the hallmark of aggressive cancers. We show that global changes in chromatin structure and chromatin accessibility in prostate tumour tissue can define castrate-resistant prostate cancer and be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor overexpression alone, w...

There is a variety of adrenocortical tumors that can be responsible for different cortisol excess levels. Genomics allowed recently many progress in this field. Exome sequencing allowed to identify somatic activating mutations of the catalytic subunit of PKA (PRKACA) in cortisol secreting adenomas responsible for overt-Cushing. Combining pangenomic snp analysis and whole genome sequencing led to the identification of inactivating germline mutations of a new tumor supp...