Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma

We are indebted to the patients for donating tumor specimens as part of this study. The authors thank the Centre de Ressources Biologiques (CRB)-Santé of Rennes (BB-0033-00056) for patient samples, Queen Mary University of London Genome Centre for Illumina Miseq sequencing, and the support by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London for Illumina Hiseq sequencing. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was supported by grants from the Kay Kendall Leukaemia Fund (KKL 757 awarded to J.O.), Cancer Research UK (22742 awarded to J.O., 15968 awarded to J.F., Clinical Research Fellowship awarded to S.A.), Bloodwise through funding of the Precision Medicine for Aggressive Lymphoma (PMAL) consortium, Centre for Genomic Health, Queen Mary University of London, Carte d’Identité des Tumeurs (CIT), Ligue National contre le Cancer, Pôle de biologie hospital universitaire de Rennes, CRB-Santé of Rennes (BB-0033-00056), and CeVi/Carnot program

The three-dimensional organization of telomeres in the nucleus of mammalian cells

BACKGROUND: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells. RESULTS: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed. CONCLUSIONS: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine

Re-establishing the ‘outsiders’: English press coverage of the 2015 FIFA Women’s World Cup

In 2015, the England Women’s national football team finished third at the Women’s World Cup in Canada. Alongside the establishment of the Women’s Super League in 2011, the success of the women’s team posed a striking contrast to the recent failures of the England men’s team and in doing so presented a timely opportunity to examine the negotiation of hegemonic discourses on gender, sport and football. Drawing upon an ‘established-outsider’ approach, this article examines how, in newspaper coverage of the England women’s team, gendered constructions revealed processes of alteration, assimilation and resistance. Rather than suggesting that ‘established’ discourses assume a normative connection between masculinity and football, the findings reveal how gendered ‘boundaries’ were both challenged and protected in newspaper coverage. Despite their success, the discursive positioning of the women’s team as ‘outsiders’, served to (re)establish men’s football as superior, culturally salient and ‘better’ than the women’s team/game. Accordingly, we contend that attempts to build and, in many instances, rediscover the history of women’s football, can be used to challenge established cultural representations that draw exclusively from the history of the men’s game. In such instances, the 2015 Women’s World Cup provides a historical moment from which the women’s game can be relocated in a context of popular culture

The politics of vibrant matter: consistency, containment and the concrete of Mussolini’s bunker

This article explores the idea of how vibrancy can be produced. Specifically, the attempt is to investigate the multiplicities of vibrancy by considering one of Mussolini’s bunkers. The author examines the location of the bunker in the EUR (Esposizione Universale Romana) neighbourhood in Rome, the bunker’s materiality, and the context and social meaning of the bunker through a contemporary art exhibition called ‘Confronti’ (Confrontations) that took place in the bunker in 2009. The article argues that while emphasizing matter’s inherent vibrancy may be useful in some cases, there is also merit in further unpacking the ways in which vibrancy is produced. In this example, the concrete bunker expresses vibrancy through the processes involved in the emergent material form, and in the sustained politics and social considerations embedded in valuing tangible urban heritage

Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age-and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance-based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall-Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (Peer reviewe

Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreati