Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Back-End Cap of the PlasPi TDM

Design of the closure used to seal the back opening of the housing of the PlasPi TDM

Source file repository PlasPi TDM

Contains All design files of PlasPi TD

Natural history of gastrointestinal manifestations in vascular Ehlers–Danlos syndrome: A 17‐year retrospective review

International audienc

Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: a review

International audienceAldosterone hypersecretion in primary aldosteronism is unilateral (aldosterone producing adenoma and primary unilateral hyperplasia) or bilateral (idiopathic adrenal hyperplasia). Laparoscopic adrenalectomy is nowadays the preferred approach to treat patients with unilateral primary aldosteronism. We review the outcomes of this intervention in recently published series. Laparoscopic adrenalectomy has a morbidity of 5-14%, mortality below 1%, and a mean hospital stay around 3 days. It generally results in the normalization of aldosterone secretion and in a large decrease of blood pressure and antihypertensive medication, but normotension without treatment is only achieved in 42% of all cases. Normotension following adrenalectomy is more likely in young and lean women with recent low grade hypertension than in obese men with long-standing high grade hypertension or a family history of hypertension. However, individual prediction of the blood pressure outcome is not accurate and predictors of hypertension cure should not be used to select patients for surgery. Age, associated health conditions and preferences of the patient are more relevant to this end

Natural History and Surgical Management of Colonic Perforations in Vascular Ehlers-Danlos Syndrome: A Retrospective Review

International audienc

PlasPi TDM: Augmentation of a low-cost camera platform for advanced underwater physical-ecological observations

Marine ecosystem dynamics in the context of climate change is a growing scientific, political and social concern requiring regular monitoring through appropriate observational technologies and studies. Thus, a wide range of tools comprising chemical, biogeochemical, physical, and biological sensors, as well as other platforms exists for marine monitoring. However, their high acquisition and maintenance costs are often a major obstacle, especially in low-income developing countries. We designed an advanced low-cost synoptic marine ecosystem observation system that operates at relatively high temporal frequencies, named PlasPi TDM. This instrument is an improved version of the camera system (PlasPI marine cameras) developed in 2020 by Autun Purser from the Alfred Wegener Institute Helmholtz Center for Polar and Marine Research (Germany), and collaborators. It incorporates several innovative developments such as multispectral (records the spectrum of any object photographed), temperature and pressure sensors. The PlasPi TDM operates to a depth of 200 m. The various field deployments demonstrate the operational capability of the PlasPi TDM for different applications and illustrate its considerable potential for in-situ observations and marine surveillance in Africa. This device is intended as an open-source project and its continued development is encouraged for a more integrated, sustainable and low-cost ocean observing system

Frequent mutations of hepatocyte nuclear factor 1 in colorectal cancer with microsatellite instability

Background & Aims: The TCF1 gene encoding hepatocyte nuclear factor 1alpha (HNF1), a transcription factor germline mutated in patients with maturity-onset diabetes of the young type 3, was recently found to be frequently inactivated by biallelic alterations in liver adenoma and in rare hepatocellular carcinomas. The impact of HNF1 in colorectal carcinogenesis has not been studied until now. Colorectal cancer is characterized by the existence of different molecular mechanisms known as microsatellite stable or unstable tumors. Methods: At first, a series of 10 adenomas and 29 colon cancers regardless of microsatellite instability status were screened for TCF1 mutations on the entire coding sequence. Results: Three mutations in microsatellite instability high (MSI-H) tumors were found in the exon 4 polymorphic poly-cytosin (C)(8) or (C)(9) tract and consisted of a cytosin deletion at position 291. To further characterize the prevalence of TCF1 mutations in the subgroup of MSI-H tumors, 52 additional MSI-H samples were screened for exon 4 alterations; 23% of MSI-H tumors (95% confidence interval, 14%-36%) were found to harbor frameshift at the poly-cytosin tract. The (C)(9) allele was significantly more frequently mutated than the (C)(8) allele (22% vs. 8%; P = 0.03), showing a higher instability of the longer repetition. Conclusions: These results show a role for HNF1 in MSI-H colorectal carcinogenesis