AXIN genetic analysis in adrenocortical carcinomas updated.

Background: Wnt/β-catenin signaling pathway activation plays an important role in adrenocortical tumorigenesis, but is only in part related to β-catenin activating somatic mutations. Recently, genetic alteration in AXIN2, a key component of the Wnt/β-catenin signaling pathway, has been described in adrenocortical tumors and specifically in adrenocortical carcinoma (ACC).

Aim: To assess frequency and consequences of AXIN genes alteration on a large cohort of ACC.

Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients.

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Local and distant recurrences occur in a subset of tumors classified as 'aggressive' ACC (aACC), as opposed to 'non-aggressive' ACC (naACC). In this study, we investigated whether tissue and serum microRNAs (miRNAs) are predictive of ACC prognosis.

SDH mutations establish a hypermethylator phenotype in paraganglioma.

Paragangliomas are neuroendocrine tumors frequently associated with mutations in RET, NF1, VHL, and succinate dehydrogenase (SDHx) genes. Methylome analysis of a large paraganglioma cohort identified three stable clusters, associated with distinct clinical features and mutational status. SDHx-related tumors displayed a hypermethylator phenotype, associated with downregulation of key genes involved in neuroendocrine differentiation.

Carney complex.

Carney complex is a rare, dominantly inherited multiple endocrine neoplasia syndrome, affecting endocrine glands as the adrenal cortex (causing Cushing's syndrome), the pituitary and the thyroid. It is associated with many other nonendocrine tumors, including cardiac myxomas, testicular tumors, melanotic schwannoma, breast myxomatosis, and abnormal pigmentation (lentiginosis) or myxomas of the skin. The gene located on the CNC1 locus was identified 12 years ago as the regulatory subunit 1A (R1A) of the protein kinase A (PRKAR1A) located at 17q22-24.

Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS).

Identification of gene expression profiles associated with cortisol secretion in adrenocortical adenomas.

Context: The cortisol secretion of adrenocortical adenomas can be either subtle or overt. The mechanisms leading to the autonomous hypersecretion of cortisol are unknown.

Objective: The objective of the study was to identify the gene expression profile associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas.

Silencing mutated β-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R.

Context: Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating β-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target.

Management of hyperglycaemia in Cushing's disease: experts' proposals on the use of pasireotide.

Cushing's disease causes considerable morbidity and mortality, including cardiovascular, metabolic, respiratory and psychiatric complications, bone demineralization and increased susceptibility to infections. Metabolic complications include a high prevalence of impaired glucose tolerance, fasting hyperglycaemia and diabetes. Although pituitary surgery is the gold-standard treatment, other treatment strategies such as radiotherapy and medical therapy to reduce cortisol synthesis may be proposed in the event of recurrence or failure, or when surgery is not an option.

Mitotane therapy in adrenocortical cancer induces CYP3A4 and inhibits 5α-reductase, explaining the need for personalized glucocorticoid and androgen replacement.

Context: Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumor. Mitotane is considered an adrenolytic substance, but there is limited information on distinct effects on steroidogenesis. However, adrenal insufficiency and male hypogonadism are widely recognized side effects of mitotane treatment.

Identification of a CpG island methylator phenotype in adrenocortical carcinomas.

Purpose: DNA methylation is a mechanism for gene expression silencing in cancer. Limited information is available for adrenocortical tumors. Abnormal methylation at the IGF2/H19 locus is common in adrenocortical carcinomas.

Phosphodiesterase 11A (PDE11A) gene defects in patients with acth-independent macronodular adrenal hyperplasia (AIMAH): functional variants may contribute to genetic susceptibility of bilateral adrenal tumors.

Context: Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. PDE11A function has been linked to predisposition to adrenocortical tumors.

Objective: The aim of the study was to study the PDE11A gene in a large cohort of patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in control subjects.

Somatic NF1 inactivation is a frequent event in sporadic pheochromocytoma.

Germline mutations in the RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127, NF1 or VHL genes are identified in about 30% of patients with pheochromocytoma or paraganglioma and somatic mutations in RET, VHL or MAX genes are reported in 17% of sporadic tumors. In the present study, using mutation screening of the NF1 gene, mapping of chromosome aberrations by single nucleotide polymorphism (SNP) array, microarray-based expression profiling and immunohistochemistry (IHC), we addressed the implication of NF1 somatic alterations in pheochromocytomas and paragangliomas. We studied 53 sporadic tumors, selected because of their classification with RET/NF1/TMEM127-related tumors by genome wide expression studies, as well as a second set of 11 independent tumors selected on their low individual levels of NF1 expression evaluated by microarray.

Laparoscopic adrenalectomy for adrenocortical carcinoma: a medico-surgical perspective.

Background: Adrenocortical carcinoma (ACC) is a rare tumor carrying a dismal prognosis. The only hope for cure is a complete surgical resection. Whether this can be achieved by laparoscopic adrenalectomy (LA) remains questionable, and is now a "hot topic" for the medical and surgical community.

Analysis of the role of Igf2 in adrenal tumour development in transgenic mouse models.

Adrenal cortical carcinomas (ACC) are rare but aggressive tumours associated with poor prognosis. The two most frequent alterations in ACC in patients are overexpression of the growth factor IGF2 and constitutive activation of Wnt/β-catenin signalling. Using a transgenic mouse model, we have previously shown that constitutive active β-catenin is a bona fide adrenal oncogene.

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center.

Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first- or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD.

Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients.

Protein kinase A alterations in endocrine tumors.

Various molecular and cellular alterations of the cyclic adenosine monophosphate (cAMP) pathway have been observed in endocrine tumors. Since protein kinase A (PKA) is a central key component of the cAMP pathway, studies of the alterations of PKA subunits in endocrine tumors reveal new aspects of the mechanisms of cAMP pathway alterations in human diseases. So far, most alterations have been observed for the regulatory subunits, mainly PRKAR1A and to a lower extent, PRKAR2B.

Epithelial to mesenchymal transition is activated in metastatic pheochromocytomas and paragangliomas caused by SDHB gene mutations.

Context: Pheochromocytoma and paraganglioma are rare neural-crest-derived tumors. They are metastatic in 15% of cases, and the identification of a germline mutation in the SDHB gene is a predictive risk factor for malignancy and poor prognosis. To date, the link between SDHB mutations and malignancy is still missing.

MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.

Purpose: Pheochromocytomas (PCC) and paragangliomas (PGL) are genetically heterogeneous neural crest-derived neoplasms. Recently we identified germline mutations in a new tumor suppressor susceptibility gene, MAX (MYC-associated factor X), which predisposes carriers to PCC. How MAX mutations contribute to PCC/PGL and associated phenotypes remain unclear.

TMEM127 screening in a large cohort of patients with pheochromocytoma and/or paraganglioma.

Context: TMEM127 is a novel pheochromocytoma (PCC) susceptibility gene.

Objectives: Our aim was to clearly determine the indications for TMEM127 genetic testing in patients with PCC and/or paraganglioma (PGL).

Patients And Methods: Germline DNA from 642 unrelated patients who did not carry mutations in major PCC susceptibility genes was analyzed.

Identification of novel genetic variants in phosphodiesterase 8B (PDE8B), a cAMP-specific phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumours.

Background: Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions.

Objective: To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours.

An interdisciplinary learning experience in neuro-optics.

How can a Ph.D. student initially trained as a biologist take part in the development of a multineuronal recording method that requires cross interaction between physics, neurobiology and mathematics? Beyond student training in the laboratory, interdisciplinary research calls for a new style of academic training of young researchers.

Reproducibility and performance of one or two samples of salivary cortisol in the diagnosis of Cushing's syndrome using an automated immunoassay system.

The purpose of this article is to evaluate the variability and reproducibility of late night salivary cortisol (LNSC) using electrochemiluminescence immunoassay (ECLIA) and compare the accuracy of one or two samples in diagnosis of Cushing's syndrome (CS). We prospectively included 64 healthy volunteers (HV), 35 patients with clinically suspected CS (S), and 26 patients with confirmed CS. Nine patients in the CS group had 24-h urinary free cortisol (UFC) less than two times the upper limit of normal (mild CS).