Résumé
INTRODUCTION: Clear cell renal cell carcinomas (ccRCCs) are highly metastatic tumors with metastases detected at diagnosis (synchronous) or during follow-up (metachronous). To date, there have been no reports comparing primary ccRCC of patients with synchronous and metachronous metastases, who are different in terms of prognosis. Determining whether there is a phenotypic difference between these 2 groups could have important clinical implications.
PATIENTS AND METHODS: In a retrospective consecutive cohort of 98 patients with ccRCC, 48 patients had metastases, including 28 synchronous and 20 metachronous presentations, with a follow-up of 10 years. For each primary tumor in these metastatic patients, pathologic criteria, expression of vascular endothelial growth factor, partitioning-defective 3, CAIX, and programmed death ligand 1 as detected by immunohistochemistry, and complete VHL status were analyzed. Univariate analysis was performed, and survival was assessed using Kaplan-Meier curves compared by log-rank test.
RESULTS: Compared with primary ccRCC in patients with metachronous metastases, primary ccRCC in patients with synchronous metastases were significantly associated with a poorer Eastern Cooperative Oncology Group performance (P = .045), higher pT status (P = .038), non-inactivated VHL gene (P = .01), sarcomatoid component (P = .007), expression of partitioning-defective 3 (P = .007), and overexpressions of vascular endothelial growth factor (> 50%) (P = .017) and programmed death ligand 1 (P = .019). Patients with synchronous metastases had a worse cancer-specific survival than patients with metachronous metastases even from metastatic diagnosis (median survival, 16 months vs. 46 months, respectively; P = .01).
CONCLUSION: This long-term study is the first to support the notion that synchronous m-ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.
Auteurs, date et publication :
Auteurs Solene-Florence Kammerer-Jacquet , Angelique Brunot , Adelaide Pladys , Guillaume Bouzille , Julien Dagher , Sarah Medane , Benoit Peyronnet , Romain Mathieu , Gregory Verhoest , Karim Bensalah , Julien Edeline , Brigitte Laguerre , Alexandra Lespagnol , Jean Mosser , Frederic Dugay , Marc-Antoine Belaud-Rotureau , Nathalie Rioux-Leclercq
Publication : Clinical Genitourinary Cancer
Date : 2017
Volume : 15
Issue : 1
Pages : e1-e7
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
The human pathogen Staphylococcus aureus expresses a set of transcriptional factors and small RNAs (sRNAs) to adapt to environmental variations. Recent harmonization of staphylococcal sRNA data allowed us to search for novel sRNAs using DETR’PROK, a computational pipeline for identifying sRNA in prokaryotes. We performed RNA-Seq on Newman strain and identified a set of 48 sRNA candidates. To avoid bioinformatic artefacts, we applied a series of cut-offs and tested experimentally each selected intergenic region. This narrowed the field to 24 expressed sRNAs, of which 21 were new and designated with Srn identifiers. Further examination of these loci revealed that one exhibited an unusual condensed sRNA cluster of about 650 nucleotides. We determined the transcriptional start sites within this region and demonstrated the presence of three contiguous sRNA genes (srn_9342, srn_9344 and srn_9345) expressed from the positive strand, and two others (srn_9343 and srn_9346) transcribed from the opposite one. Using comparative genomics, we showed that genetic organization of the srn_9342-9346 locus is specific to Newman and that its expression is growth-phase dependent and subjected to nutrient deprivation and oxidative stress. Finally, we demonstrated that srn_9343 encodes a secreted peptide that could belong to a novel S. aureus toxin-antitoxin system.
Auteurs, date et publication :
Auteurs Julie Bronsard , Gaetan Pascreau , Mohamed Sassi , Tony Mauro , Yoann Augagneur , Brice Felden
Publication : Scientific Reports
Date : 2017
Volume : 7
Issue : 1
Pages : 4565
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Agriculture is undergoing important changes in order to meet sustainable soil management with respect to biodiversity (namely agroecology). Within this context, alternative solutions to mineral fertilizers such as agricultural biostimulants are thus promoted and being developed. The mechanisms by which some soil biostimulants sustain soil biological functioning and indirectly increase crop yields are still unknown. Our goal in the present study was to demonstrate if and to what extent the application of a soil biostimulant affects the soil heterotrophic microbial communities that are involved in organic matter decomposition and carbon mineralization. We hypothesized that the addition of a biostimulant results in changes in the composition and in the biomass of soil microbial communities. This in turn increases the mineralization of the organic matter derived from crop residues. We performed soil microcosm experiments with the addition of crop residues and a biostimulant, and we monitored the organic carbon (orgC) mineralization and the microbial biomass, along with the microbial community composition by sequencing 16S rRNA gene and ITS amplicons. The addition of a soil biostimulant caused a pH neutralizing effect and simultaneous enhancement of the orgC mineralization of crop residues (+ 400 μg orgC g-1 dry soil) and microbial biomass (+ 60 μg orgC g-1 dry soil) that were linked to changes in the soil microbial communities. Our findings suggest that the soil carbon mineralization enhancement in the presence of the biostimulant was supported by the specific recruitment of soil bacteria and fungi. Whereas archaea remained stable, several operational taxonomic units (OTUs) of indigenous soil bacteria and fungi were enriched and affiliated with known microbial decomposers such as Cytophagaceae, Phaselicystis sp., Verrucomicrobia, Pseudomonas sp., Ramicandelaber sp., and Mortierella sp., resulting in lower soil microbial richness and diversity.
Auteurs, date et publication :
Auteurs Eve Hellequin , Cécile Monard , Achim Quaiser , Morgane Henriot , Olivier Klarzynski , Françoise Binet
Publication : PLOS ONE
Date : 2025
Volume : 13
Issue : 12
Pages : e0209089
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Nitrogen fixation in the legume root-nodule symbiosis has a critical importance in natural and agricultural ecosystems and depends on the proper choice of the symbiotic partners. However, the genetic determinism of symbiotic specificity remains unclear. To study this process, we inoculated three Lupinus species (L. albus, L. luteus, L. mariae-josephae), belonging to the under-investigated tribe of Genistoids, with two Bradyrhizobium strains (B. japonicum, B. valentinum) presenting contrasted degrees of symbiotic specificity depending on the host. We produced the first transcriptomes (RNA-Seq) from lupine nodules in a context of symbiotic specificity. For each lupine species, we compared gene expression between functional and non-functional interactions and determined differentially expressed (DE) genes. This revealed that L. luteus and L. mariae-josephae (nodulated by only one of the Bradyrhizobium strains) specific nodulomes were richest in DE genes than L. albus (nodulation with both microsymbionts, but non-functional with B. valentinum) and share a higher number of these genes between them than with L. albus. In addition, a functional analysis of DE genes highlighted the central role of the genetic pathways controlling infection and nodule organogenesis, hormones, secondary, carbon and nitrogen metabolisms, as well as the implication of plant defence in response to compatible or incompatible Bradyrhizobium strains.
Auteurs, date et publication :
Auteurs J. Keller , J. Imperial , T. Ruiz-Argüeso , K. Privet , O. Lima , S. Michon-Coudouel , M. Biget , A. Salmon , A. Aïnouche , F. Cabello-Hurtado
Publication : Plant Science
Date : 2018
Volume : 266
Pages : 102-116
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Genome duplication is essential for cell proliferation, and the mechanisms regulating its execution are highly conserved. These processes give rise to a spatiotemporal organization of replication initiation across the genome, referred to as the replication program. Despite the identification of such programs in diverse eukaryotic organisms, their biological importance for cellular physiology remains largely unexplored. We address this fundamental question in the context of genome maintenance, taking advantage of the inappropriate origin firing that occurs when fission yeast cells lacking the Rad3/ATR checkpoint kinase are subjected to replication stress. Using this model, we demonstrate that the replication program quantitatively dictates the extent of origin de-regulation and the clustered localization of these events. Furthermore, our results uncover an accumulation of abnormal levels of single-stranded DNA (ssDNA) and the Rad52 repair protein at de-regulated origins. We show that these loci constitute a defining source of the overall ssDNA and Rad52 hotspots in the genome, generating a signature pattern of instability along the chromosomes. We then induce a genome-wide reprogramming of origin usage and evaluate its consequences in our experimental system. This leads to a complete redistribution of the sites of both inappropriate initiation and associated Rad52 recruitment. We therefore conclude that the organization of genome duplication governs the checkpoint control of origin-associated hotspots of instability and plays an integral role in shaping the landscape of genome maintenance.
Auteurs, date et publication :
Auteurs Blanca Gómez-Escoda , Pei-Yun Jenny Wu
Publication : Genome Research
Date : 2018
Volume : 28
Issue : 8
Pages : 1179-1192
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. Previously, we reported a gene expression signature related to tumor infiltration. Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma. As EMX2 is reported to play a role in carcinogenesis, we investigated the impact of EMX2 overexpression in glioma-related cell lines.
Auteurs, date et publication :
Auteurs Annabelle Monnier , Rachel Boniface , Régis Bouvet , Amandine Etcheverry , Marc Aubry , Tony Avril , Véronique Quillien , Eric Chevet , Jean Mosser
Publication : BMC Cancer
Date : 2018
Volume : 18
Issue : 1
Pages : 1213
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
In the processes controlling ecosystem fertility, fungi are increasingly acknowledged as key drivers. However, our understanding of the rules behind fungal community assembly regarding the effect of soil fertility level remains limited. Using soil samples from typical tea plantations spanning c. 2167 km north-east to south-west across China, we investigated the assemblage complexity and assembly processes of 140 fungal communities along a soil fertility gradient. The community dissimilarities of total fungi and fungal functional guilds increased with increasing soil fertility index dissimilarity. The symbiotrophs were more sensitive to variations in soil fertility compared with pathotrophs and saprotrophs. Fungal networks were larger and showed higher connectivity as well as greater potential for inter-module connection in more fertile soils. Environmental factors had a slightly greater influence on fungal community composition than spatial factors. Species abundance fitted the Zipf–Mandelbrot distribution (niche-based mechanisms), which provided evidence for deterministic-based processes. Overall, the soil fungal communities in tea plantations responded in a deterministic manner to soil fertility, with high fertility correlated with complex fungal community assemblages. This study provides new insights that might contribute to predictions of fungal community complexity.
Auteurs, date et publication :
Auteurs Junjie Guo , Ning Ling , Zhaojie Chen , Chao Xue , Ling Li , Lisheng Liu , Limin Gao , Min Wang , Jianyun Ruan , Shiwei Guo , Philippe Vandenkoornhuyse , Qirong Shen
Publication : New Phytologist
Date : 2025
Volume : 226
Issue : 1
Pages : 232-243
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Dispersal limitation may drive the structure of fungal microbiota of plant roots at small spatial scales. Fungal root microorganisms disperse through the plant rooting systems from hosts to hosts. Due to a pronounced host-preference effect, the composition of endophytic root microbiota may follow plant distribution. A given plant community may hence include a matrix of host-plant species that represent various habitat permeabilities to fungal dispersal in the floristic landscape. We experimentally tested the effect of host-plant isolation on endophytic fungal assemblages (Ascomycota, Basidiomycota, Glomeromycotina) inhabiting Brachypodium pinnatum roots. We calculated host-plant isolation using Euclidean distance (distance-based dispersal limitation) and resistance distance (functional-based dispersal limitation), based on host presences. All fungal groups were more influenced by the resistance distance between B. pinnatum than by the Euclidean distance. Fungal dispersal was hence strongly related to the spatial distribution of the host plants. The fungal groups displayed however different responses (in richness, abundance, and composition) to host isolation. Additionally, fungal assemblages were more strongly controlled by the degree of connectivity between host plants during the prior year than by current connectivity. This discrepancy may be due to changes in plant species coverage in a year and/or to the delay of dispersal response of fungi. This study it the first to demonstrate how small-scale host-plant distributions mediate connectivity in microorganisms. The consequences of plant distributions for the permeability of the floristic landscape to fungi dispersal appear to control fungal assemblages, but with possibly different mechanisms for the different fungal groups.
Auteurs, date et publication :
Auteurs Cendrine Mony , Nathan Vannier , Philomène Brunellière , Marine Biget , Sophie Coudouel , Philippe Vandenkoornhuyse
Publication : Ecology
Date : 2025
Volume : 101
Issue : 4
Pages : e02976
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Plant roots are inhabited by a diversity of microorganisms known to be key drivers of plant growth and health. Although the rules governing root microbiota assembly have been investigated and the importance of abiotic determinants highlighted, the consequences of the biotic context of the plant community have often been overlooked. We tested the hypothesis that the abundance of species in a given plant neighborhood could leave a fingerprint on its root-endophytic fungal community, ultimately impacting its biomass. Outdoor experimental mesocosms, comprising a range of floristic compositions and spatially mapped plant distributions, were monitored for 2y. Medicago truncatula was used as trap-plant and grown under standardized conditions on soil samples collected in the mesocosms. The root-endophytic fungal community of M. truncatula was described by amplicon mass sequencing and M. truncatula performance was also assessed. The richness and evenness of M. truncatula's root-endophytic fungal community were explained by the small-scale plant neighborhood of the soil samples. For instance, the occurrence of Brachypodium pinnatum in the neighborhood induced higher and lower richness of Sordariomycetes and Glomeromycetes, respectively, whereas Holcus mollis decreased the OTU evenness of the entire mycobiota. These changes in fungal clade OTU richness and evenness were related to modifications in the biomass of M. truncatula. These results indicate that a given plant endophytic fungal community is determined in part by the neighboring plants. Considering that changes in endophytic fungal community are correlated with the plant biomass, this suggests that plant-plant interactions (i.e. competition, facilitation) impacting plant biomass can be mediated by endophytic fungal community changes.
Auteurs, date et publication :
Auteurs Nathan Vannier , Anne-Kristel Bittebiere , Cendrine Mony , Philippe Vandenkoornhuyse
Publication : Fungal Ecology
Date : 2020
Volume : 44
Pages : 100907
Catégorie(s)
#CNRS #EcoGenO #Université de RennesRésumé
Cell identity relies on the cross-talk between genetics and epigenetics and their impact on gene expression. Oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) is the first step of an active DNA demethylation process occurring mainly at enhancers and gene bodies and, as such, participates in processes governing cell identity in normal and pathological conditions. Although genetic alterations are well documented in multiple myeloma (MM), epigenetic alterations associated with this disease have not yet been thoroughly analyzed. To gain insight into the biology of MM, genome-wide 5hmC profiles were obtained and showed that regions enriched in this modified base overlap with MM enhancers and super enhancers and are close to highly expressed genes. Through the definition of a MM-specific 5hmC signature, we identified FAM72D as a poor prognostic gene located on 1q21, a region amplified in high risk myeloma. We further uncovered that FAM72D functions as part of the FOXM1 transcription factor network controlling cell proliferation and survival and we evidenced an increased sensitivity of cells expressing high levels of FOXM1 and FAM72 to epigenetic drugs targeting histone deacetylases and DNA methyltransferases.
Auteurs, date et publication :
Auteurs Fabrice Chatonnet , Amandine Pignarre , Aurélien A. Sérandour , Gersende Caron , Stéphane Avner , Nicolas Robert , Alboukadel Kassambara , Audrey Laurent , Maud Bizot , Xabier Agirre , Felipe Prosper , José I. Martin-Subero , Jérôme Moreaux , Thierry Fest , Gilles Salbert
Publication : Haematologica
Date : 2020
Volume : 105
Issue : 3
Pages : 774-783