Laser-induced damage thresholds of high-reflective coatings for PW lasers

International audienc

Ultra-short pulse laser-induced damage thresholds of broadband high-reflective and low dispersive coatings

International audienc

Thin films characterizations to design high-reflective coatings for ultrafast high power laser systems

International audienc

Développement de composants optiques de grande taille pour laser multi-PW

National audienc

Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers.

Extra-cranial rhabdoid tumors (RT) are highly aggressive malignancies of infancy, characterized by undifferentiated histological features and loss of SMARCB1 expression. The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC). Moreover, late cases occurring in adults are now increasingly reported, raising the question of differential diagnoses and emphasizing nosological issues. To address this issue, we have analyzed the expression profiles of a training set of 32 SMARCB1-deficient tumors (SDT), with ascertained diagnosis of RT (n = 16, all 10 years of age), UC (n = 3) and RMC (n = 5). As compared with other SDT, RT are characterized by an embryonic signature, and up-regulation of key-actors of de novo DNA methylation processes. Using this signature, we then analysed the expression profiling of 37 SDT to infer the appropriate diagnosis. Thirteen adult onset tumors showed strong similarity with pediatric RT, in spite of older age; by exome sequencing, these tumors also showed genomic features indistinguishable from pediatric RT. In contrary, 8 tumors were reclassified within carcinoma, ES or UC categories, while the remaining could not be related to any of those entities. Our results demonstrate that embryonic signature is shared by all RT, whatever the age at diagnosis; they also illustrate that many adult-onset SDT of ambiguous histological diagnosis are clearly different from RT. Finally, our study paves the way for the routine use of expression-based signatures to give accurate diagnosis of SDT

Participation du laser YAG pulse en assistance a un usinage conventionnel sur des materiaux type ceramique

Available at INIST (FR), Document Supply Service, under shelf-number : AR 14103 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma

Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.The following associations supported this work: Courir pour Mathieu, Dans les pas du Géant, Olivier Chape, Les Bagouzamanon, Enfants et Santé, and les Amis de Claire. The study was performed in the context of the following European Union consortia: Euro Ewing (grant agreement no. 602856), BLUEPRINT (grant agreement no. 282510), PROVABES (grant agreement no. 01KT1310), ASSET (grant agreement no. 259348), and TECHNOBEAT (grant agreement no. 668724). N.C.S. was supported by a long-term fellowship of the Human Frontier Science Program (LT000211/2014). J.K. was supported by a DOC Fellowship of the Austrian Academy of Sciences. D. Surdez was supported by the Institut Curie-SIRIC (Site de Recherche Intégrée en Cancérologie) program. E.d.A. was supported by Ministry of Economy and Competitiveness of Spain-FEDER grants (CIBERONC, RD12/0036/0017, PI14/01466), María García-Estrada, CRIS contra el Cáncer Foundations, and Pablo Ugarte Association. C.B. was supported by a New Frontiers Group award of the Austrian Academy of Sciences and by a European Research Council (ERC) Starting Grant (European Union's Horizon 2020 research and innovation program; grant 679146). E.M.T. was supported by fellowships of the Austrian Science Fund (FWF, Lise Meitner Fellowship M1448-B13; and Elise Richter Fellowship V506-B28)

{DNA} methylation heterogeneity defines a disease spectrum in {Ewing} sarcoma

Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine