12 research outputs found
Abstract 2389: LINE-1 tumor hypomethylation is associated with shorter recurrence-free survival in localized clear-cell renal cell carcinoma
No full textAbstract
Background: Cancer cells are characterized by alterations of DNA methylation patterns involving global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Global DNA hypomethylation is thought to play a role in genetic instability and tumor aggressiveness. Long interspersed nucleotide element-1 (L1/LINE-1) repetitive elements represent 40% of the genome and their methylation is a good indicator of the global DNA methylation level. Although LINE-1 methylation has been previously shown to be associated with prognosis of patients with cancer, the value of LINE-1 methylation in predicting recurrence of patients with localized clear-cell renal cell carcinomas remains unknown.
Material and Methods: We quantified the LINE-1 methylation using bisulfite pyrosequencing in cohort of 200 patients with resected clear-cell renal cell carcinomas (AJCC stage I-III). LINE-1 methylation of adjacent normal kidney was also assessed in 128 cases. Threshold of tumor LINE-1 hypomethylation was defined as LINE-1 methylation in normal samples minus three standard deviation.
Results: Median methylation of tumor samples was 59.01% versus 61.61% for normal adjacent kidney samples (p<10-5). LINE-1 methylation level of normal adjacent kidney was associated with tumor size (Spearman R=0.21, P=0.02) but not with age (p=0.24) or Leibovitch score (p=0.05). Tumor LINE-1 hypomethylation was observed in 20 samples (n=10%). Strikingly, those were enriched for tumors occurring in female (60% versus 27.7%) (p=0.005); of note, no association was found between LINE-1 tumor hypomethylation and tumor grade (p=0.31), stage (p=1), age (p=0.24) and Leibovitch score (p=0.82). In multivariate analysis, only Leibovitch score and LINE-1 hypomethylation were independently associated with poor recurrence-free survival.
Conclusion: LINE-1 hypomethylation is associated with shorter recurrence-free survival in patients with resected clear-cell renal cell carcinomas, suggesting the possibility of using it as predictive biomarker of recurrence.
Citation Format: Gabriel G. Malouf, Roger Mouawad, Frederick Allanic, Eva Compérat, Morgan Roupret, David Khayat, Jean-Philippe Spano. LINE-1 tumor hypomethylation is associated with shorter recurrence-free survival in localized clear-cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2389. doi:10.1158/1538-7445.AM2017-2389</jats:p
漫谈对外"理性识字法"的构造
No full textInternational audienceThis paper presents the primary results of research on Chinese characters teaching of Chinese as maternal language and Chinese as a foreign language. In China, the teaching of characters has a long history and has accumulated precious experiences. The author especially studied the method of teaching characters in the Mass Education movement (pingmin jiaoyu) of the years 1920-1927, and the “regrouped character teaching” (jizhong shizi) created in 1958 for primary schools. He insists on the answers these methods have given to two main questions: 1. How many characters must a student learn in order to be able to read? 2. How is it possible to teach characters in a “reasoned ”way, respecting the rules of the graphic composition of the characters and using the most efficient way for a student to memorize them?“理性识字法”就是一种既体现汉语汉字的特点，又符合学习者的学习策略以及认知规律的识字方法。本论文谈到怎么能构造这类的方法。作者引用一些中国母语的识字法经验，尤其是第二十世纪20年代扫盲教育使用的一些识字课本以及目前还行之有效的小学集中识字方法
漫谈对外"理性识字法"的构造
No full textInternational audienceThis paper presents the primary results of research on Chinese characters teaching of Chinese as maternal language and Chinese as a foreign language. In China, the teaching of characters has a long history and has accumulated precious experiences. The author especially studied the method of teaching characters in the Mass Education movement (pingmin jiaoyu) of the years 1920-1927, and the “regrouped character teaching” (jizhong shizi) created in 1958 for primary schools. He insists on the answers these methods have given to two main questions: 1. How many characters must a student learn in order to be able to read? 2. How is it possible to teach characters in a “reasoned ”way, respecting the rules of the graphic composition of the characters and using the most efficient way for a student to memorize them?“理性识字法”就是一种既体现汉语汉字的特点，又符合学习者的学习策略以及认知规律的识字方法。本论文谈到怎么能构造这类的方法。作者引用一些中国母语的识字法经验，尤其是第二十世纪20年代扫盲教育使用的一些识字课本以及目前还行之有效的小学集中识字方法
Risque de taux lié au financement d'un investissement de type ligne à grande vitesse
No full textSpecified financial risks are attached to the building of a high speed line because of:- the huge volume of necessary funding and the duration of the building phase,- the operating losses arising during the first years,- the mismatches between the life of investments and the maturity of the initial financings,- the uncertain surrounding parameters (financial market rates, inflation).These risks have consequential effects on the income statement and also on the indebtedness of the companies.The article studies, and illustrates with a quoted case, the sensitivity to these parameters. It shows that depending on the internal rate of return of such a construction, the situation in the future can appear either good or generating unlimited losses.The author examines which financial tools could allow the companies to hedge these risks.La construction d'une ligne à grande vitesse comporte des risques financiers particuliers du fait.- de l'importance des financements à réaliser et de la durée même de la construction,- des premières années d'exploitation déficitaires,- de décalages entre la durée de vie et celle des financements initiaux,- des incertitudes sur les paramètres environnants (taux des marchés financiers, inflation).Ces risques ont des impacts sur les comptes de résultats et les reports à nouveau, ainsi que sur l'endettement des entreprises.L'article étudie, sur un cas chiffré, les sensibilités à ces paramètres et montre qu'avec le taux de rentabilité interne de ce type d'ouvrage, les situations à terme peuvent être bonnes ou générer des pertes illimitées.L'auteur s'interroge sur les outils financiers qui permettraient de couvrir les entreprises contre ces risques
Embedding the personal: the construction of a 'fashion autobiography' as a museum exhibition, informed by innovative practice at ModeMuseum, Antwerp
No full textMy intention is to contribute to the field of exhibition-making a repertoire of presentation modes, previously not analysed or documented, that can be applied to the display of fashion in the museum and which will extend those techniques currently available to the exhibition-maker to create meaningful and stimulating exhibition environments.
Part 1 contextualises my investigation, through discussion of the exhibition as source material, the methods employed to execute the research and analysis of relevant literature. Part 1 concludes with an introduction to ModeMuseum, Antwerp, which is the primary location for my research.
Part 2 details the identification, description and definition of a repertoire of presentation modes, classified and distinguished as innovative through comparative analysis of over 100 exhibitions visited for this research, alongside investigation of the exhibition formats and structures that support deployment of the modes.
Part 3 relates the application of the presentation modes to the construction of a 'fashion autobiography‘ in the form of a proposal for a hypothetical exhibition, through examination of the processes utilised to develop the exhibition narrative and detailed account of the proposal in its final realisation.
In conclusion, I will critically reflect on the research executed, underlining the interrelationship of the theoretical and practice-based activities. Finally, I will detail opportunities taken to disseminate this research, and indicate possible directions for continued investigation
Abstract 116: Study of TERT promoter and FGFR3 mutations in upper-tumor urothelial carcinomas
No full textExpression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma
No full textInternational audiencePrediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression. We identified prognostic lncRNAs in a training set of 351 localized ccRCCs from The Cancer Genome Atlas and validated lncRNA-based recurrence classification in an independent cohort of 167 localized ccRCCs. We identified lncRNA MFI2-AS1 as best candidate in the training set. In the validation cohort, MFI2-AS1 expression was independently associated with shorter disease-free survival (Hazard Ratio (HR) for relapse 3.5, p = 0.0001). Combined with Leibovich classification, MFI2-AS1 status improved prediction of recurrence (C-index 0.70) compared to MFI2-AS1 alone (0.67) and Leibovich classification alone (0.66). In patients with aggressive tumors (Leibovich ≥5), MFI2-AS1 expression was associated with dramatically increased risk of relapse (HR 12.16, p < 0.0001) compared to patients with undetectable MFI2-AS1 who had favorable outcomes. Compared to normal samples, MFI2-AS1 was upregulated in tumor tissue, and higher expression was associated with metastatic dissemination. Overall, MFI2-AS1 status improves patient stratification in localized ccRCC, which supports further integration of lncRNAs in molecular cancer classifications
<i>NSD1</i> Inactivation and <i>SETD2</i> Mutation Drive a Convergence toward Loss of Function of H3K36 Writers in Clear Cell Renal Cell Carcinomas
No full textAbstract
Extensive dysregulation of chromatin-modifying genes in clear cell renal cell carcinoma (ccRCC) has been uncovered through next-generation sequencing. However, a scientific understanding of the cross-talk between epigenetic and genomic aberrations remains limited. Here we identify three ccRCC epigenetic clusters, including a clear cell CpG island methylator phenotype (C-CIMP) subgroup associated with promoter methylation of VEGF genes (FLT4, FLT1, and KDR). C-CIMP was furthermore characterized by silencing of genes related to vasculature development. Through an integrative analysis, we discovered frequent silencing of the histone H3 K36 methyltransferase NSD1 as the sole chromatin-modifying gene silenced by DNA methylation in ccRCC. Notably, tumors harboring NSD1 methylation were of higher grade and stage in different ccRCC datasets. NSD1 promoter methylation correlated with SETD2 somatic mutations across and within spatially distinct regions of primary ccRCC tumors. ccRCC harboring epigenetic silencing of NSD1 displayed a specific genome-wide methylome signature consistent with the NSD1 mutation methylome signature observed in Sotos syndrome. Thus, we concluded that epigenetic silencing of genes involved in angiogenesis is a hallmark of the methylator phenotype in ccRCC, implying a convergence toward loss of function of epigenetic writers of the H3K36 histone mark as a root feature of aggressive ccRCC. Cancer Res; 77(18); 4835–45. ©2017 AACR.</jats:p
Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny
No full textSummary: Esthesioneuroblastoma (ENB) is a rare cancer of the olfactory mucosa, with no established molecular stratification to date. We report similarities of ENB with tumors arising in the neural crest and perform integrative analysis of these tumors. We propose a molecular-based subtype classification of ENB as basal or neural, both of which have distinct pathological, transcriptomic, proteomic, and immune features. Among the basal subtype, we uncovered an IDH2 R172 mutant-enriched subgroup (∼35%) harboring a CpG island methylator phenotype reminiscent of IDH2 mutant gliomas. Compared with the basal ENB methylome, the neural ENB methylome shows genome-wide reprogramming with loss of DNA methylation at the enhancers of axonal guidance genes. Our study reveals insights into the molecular pathogenesis of ENB and provides classification information of potential therapeutic relevance. : Classe et al. report an integrative multi-omics analysis of esthesioneuroblastomas (ENBs) and identify two subgroups of ENBs: neural-like and basal-like. These subgroups are linked to cell ontogeny and are associated with distinct clinicopathological features and patient outcomes. Notably, one-third of basal ENBs harbor an IDH2 R172 mutation with a CpG island methylator phenotype. Keywords: esthesioneuroblastomas, IDH2, neural, basal, DNA methylation, sequencing, genetics, epigenetics, survival, ki6
Supplementary Table S2 from <i>NSD1</i> Inactivation and <i>SETD2</i> Mutation Drive a Convergence toward Loss of Function of H3K36 Writers in Clear Cell Renal Cell Carcinomas
No full textList of 369 probe sets defining the C-CIMP (CpG island methylator phenotype) in ccRCCs, including mean beta-values of those in C-CIMP (cluster 3) versus no-CIMP (cluster 2). Expression values as well as fold-changes of gene expression of those genes are also reported.</p
