Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation

Occlusodontie pédiatrique (dépistage et conduite à tenir)

Afin de concevoir au mieux l'intérêt d'un dépistage et d'une prise en charge précoces des anomalies occlusales et fonctionnelles, l'auteur précise tout d'abord qu'il est intéressant de comprendre les différents phénomènes de croissance osseuse du massif craniofacial, pour qu'une thérapeutique adaptée puisse être efficace dans les plus brefs délais. Puis, après avoir décrit les caractéristiques de l'occlusion physiologique en dentures temporaire et mixte, il définit l'occlusion pathologique les malocclusions et en expliquer leurs diverses conséquences. Il retient ensuite les éléments clés indispensables à l'établissement du diagnostic précoce, pour enfin éclairer le lecteur sur les conduites à tenir, préventive et interceptive, auxquelles celui-ci devrait s'initier.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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Vingt ans de transitions agricoles et rurales à l'Est. Quels enseignements? Vingt ans après la rupture systémique de 1990 et six ans après le premier élargissement de l'Union européenne à l'Est, la thématique de ce numéro double se veut être un bilan des différentes dispositions structurelles et fonctionnelles des agricultures et des politiques publiques qui se sont mises en place dans les pays d’Europe centrale et orientale. S'appuyant sur l'observation de terrains très divers, douze chercheurs se sont penchés sur les nouveaux enjeux économiques et sociaux dus aux transitions postcommunistes. Comment se sont manifestés les obstacles face à la nouvelle concurrence des marchés ? Comment s’est recomposée la ruralité ? Quels enseignements tirés des bouleversements intervenus dans tous les secteurs de la production agricole ? Les analyses par pays, sur une région ou sur un village viennent opportunément compléter les enseignements synthétiques présentés, montrant ainsi le profond renouvellement des cadres théoriques et méthodologiques. Le rôle de la politique agricole commune reste présent à chacun des niveaux. Note de lecture L’Allemagne du XXIe siècle, une nouvelle nation

Chimeric oncogene regulates the EGR2 sarcoma susceptibility gene via a GGAA-microsatellite

International audienceDeciphering the ways in which somatic mutations and germline susceptibility variants cooperate to promote cancer is challenging. Ewing sarcoma is characterized by fusions between EWSR1 and members of the ETS gene family, usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors that bind DNA at GGAA motifs. A recent genome-wide association study identified susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited proliferation, clonogenicity and spheroidal growth in vitro and induced regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the EGR2 locus in affected subjects and controls identified 291 Ewing-associated SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by converting an interspaced GGAT motif into a GGAA motif, thereby increasing the number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer activity of this sequence, with epigenetic characteristics of an active regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which increased global and allele-specific EGR2 expression. Collectively, our findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesi

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed