HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32).

International audienceThe t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation

Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT

Chromosome 9p21 gene copy number in Ewing's sarcoma family of tumour (ESFT) cell lines and primary ESFT has been evaluated using Multiplex Ligation-dependent probe amplification, and the clinical significance of CDKN2A loss and p16/p14ARF expression investigated. Homozygous deletion of CDKN2A was identified in 4/9 (44%) of ESFT cell lines and 4/42 (10%) primary ESFT; loss of one copy of CDKN2A was identified in a further 2/9 (22%) cell lines and 2/42 (5%) tumours. CDKN2B was co-deleted in three (33%) cell lines and two (5%) tumours. Co-deletion of the MTAP gene was observed in 1/9 (11%) cell lines and 3/42 (7%) tumours. No correlation was observed between CDKN2A deletion and clinical parameters. However, co-expression of high levels of p16/p14ARF mRNA predicted a poor event-free survival (P=0.046, log-rank test). High levels of p16/p14ARF mRNA did not correlate with high expression of p16 protein. Furthermore, p16 protein expression did not predict event-free or overall survival. Methylation is not a common mechanism of p16 gene silencing in ESFT. These studies demonstrate that loss (homozygous deletion or single copy) of CDKN2A was not prognostically significant in primary ESFT. However, high levels of p16/p14ARF mRNA expression were predictive of a poor event-free survival and should be investigated further

Translocation breakpoints in FHIT and FRA3B in both homologs of chromosome 3 in an esophageal adenocarcinoma

Common fragile sites have been proposed to play a mechanistic role in chromosome translocations and other rearrangements in cancer cells in vivo based on their behavior in vitro and their co-localization with cancer translocation breakpoints. This hypothesis has been the subject of controversy, because associations have been made at the chromosomal level and because of the large number of both fragile sites and cancer chromosome breakpoints. Tests of this hypothesis at the molecular level are now possible with the cloning of common fragile site loci and the use of fragile site clones in the analysis of rearranged chromosomes. FRA3B, the most frequently seen common fragile site, lies within the large FHIT gene. It is now well established that this region is the site of frequent, large intragenic deletions and aberrant transcripts in a number of tumors and tumor cell lines. In contrast, only one tumor-associated translocation involving the FHIT gene has been reported. We have found translocations in both homologs of chromosome 3 in an early-passage esophageal adenocarcinoma cell line. This cell line showed no normal FHIT transcripts by reverse transcription polymerase chain reaction. Subsequent chromosome analysis showed translocations of the short arms of both homologs of chromosome 3: t(3;16) and t(3;4). The breakpoints of both translocations were shown by fluorescence in situ hybridization and polymerase chain reaction to be in the FHIT gene, at or near the center of the fragile site region. Using rapid amplification of cDNA ends with FHIT primers, a noncoding chimeric transcript resulting from t(3;16) was identified. These data provide direct support for the hypothesis that FRA3B , and likely other common fragile sites, may be “hot spots” for translocations in certain cancers, as they are for deletions, and that such translocations have the potential to form abnormal chimeric transcripts. In addition, the results suggest selection for loss of a functional FHIT gene by the translocation events. © 2001 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35130/1/1095_ftp.pd

Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis

Ontologie, sciences cognitives et identité personnelle :

The purpose of this work is to proceed at the examination of some problems related to the nebulous but so fundamental notion of personal identity. At first, we confronted both antireductionist and reductionist views upon self identity. Then, we focalise on non eliminative reductionism. We explore respective worth of psychological and corporeal criterions. Finally, we discuss internalist and externalist conceptions of mind, and drawn out some consequences about the questions of self identity and consciousness unity. Our discussion takes end with the review and the analysis of some critics, opposed to the use of thought experiments in the scope of reflections about the self. We conclude in defining some criterions of self identity which integer, through a temporal and spatial continuity, the somatic then psychological dimension of the individual.Ce travail se propose de décortiquer quelques-uns des problèmes attenants à la notion nébuleuse et pourtant si fondamentale d'identité personnelle. Nous confrontons d'abord les perspectives antiréductionnistes et réductionnistes de l'identité personnelle. Puis, nous focalisant sur le réductionnisme non-éliminativiste, nous explorons les mérites respectifs des critères psychologiques et corporels. Enfin, nous discutons des conceptions internalistes et externalistes de l'esprit, et en dégageons les conséquences concernant les questions de l'identité personnelle et de l'unité de la conscience. Notre discussion s'achève par une présentation et analyse des critiques opposées à l'usage des expériences de pensée dans le cadre des réflexions sur le moi. Nous concluons sur la définition de critères de l'identité personnelle qui intègrent, dans une continuité temporelle et spatiale, les dimensions somatiques, puis psychologiques, de l'individu

EWSR1 (Ewing sarcoma region 1)

Review on EWSR1 (Ewing sarcoma region 1), with data on DNA, on the protein encoded, and where the gene is implicated

Ontologie, sciences cognitives et identité personnelle

Ce travail se propose de décortiquer quelques-uns des problèmes attenants à la notion nébuleuse et pourtant si fondamentale d'identité personnelle. Nous confrontons d'abord les perspectives antiréductionnistes et réductionnistes de l'identité personnelle. Puis, nous focalisant sur le réductionnisme non-éliminativiste, nous explorons les mérites respectifs des critères psychologiques et corporels. Enfin, nous discutons des conceptions internalistes et externalistes de l'esprit, et en dégageons les conséquences concernant les questions de l'identité personnelle et de l'unité de la conscience. Notre discussion s'achève par une présentation et analyse des critiques opposées à l'usage des expériences de pensée dans le cadre des réflexions sur le moi. Nous concluons sur la définition de critères de l'identité personnelle qui intègrent, dans une continuité temporelle et spatiale, les dimensions somatiques, puis psychologiques, de l'individu.The purpose of this work is to proceed at the examination of some problems related to the nebulous but so fundamental notion of personal identity. At first, we confronted both antireductionist and reductionist views upon self identity. Then, we focalise on non eliminative reductionism. We explore respective worth of psychological and corporeal criterions. Finally, we discuss internalist and externalist conceptions of mind, and drawn out some consequences about the questions of self identity and consciousness unity. Our discussion takes end with the review and the analysis of some critics, opposed to the use of thought experiments in the scope of reflections about the self. We conclude in defining some criterions of self identity which integer, through a temporal and spatial continuity, the somatic then psychological dimension of the individual.NANCY2-BU Lettres (543952103) / SudocSudocFranceF

Les Maisons de santé pluriprofessionnelles en PACA (une analyse des données territoriales et enquêtes auprès des professionnels de santé et des usagers)

INTRODUCTION: Les projets de Maisons et Pôles de Santé pluriprofessionnels se multiplient depuis 2010 mais nous manquons d'outils utiles à leur développement et suivi. Le but de notre étude est de dégager des indicateurs de faisabilité et de besoin ainsi que des outils de suivi permettant la mise en place de ces structures. METHODE: Nous étudions les 7 projets sélectionnés en PACA en octobre 2010 en croisant: _ des données socio-démographiques et territoriales; _ des résultats d'entretiens réalisés auprès des professionnels de santé et élus; _ des résultats d'une enquête menée auprès des patients. RESULTATS: Les entretiens révèlent que l'adhésion des professionnels de santé n'est pas acquise, malgré la sélection préalable des projets et mettent en relief des profils de soignants adaptés à ces projets. Dans l'enquête usagers, sur 2500 questionnaires nous avons 29% de participation. 65% des usagers sont insatisfaits de l'offre de soins de leur territoire. L'analyse territoriale confirme les données du SROS ambulatoire. DISCUSSION: Nous dégageons 10 indicateurs de besoin et 5 de faisabilité avec proposition d'un score de besoin et de faisabilité. Grâce à 3 ans de suivi nous avons identifié des indicateurs de suivi et avons élaboré une matrice de suivi, permettant l'auto-évaluation des projets. CONCLUSION: Les outils d'évaluation et de suivi proposés ici sont utilisés à ce jour pour le suivi des projets en PACA. Pour être validés ces outils doivent être expérimentés sur de plus nombreux projets. Une même étude faire après ouverture des structures permettrait d'évaluer l'impact de celles-ci sur l'accès aux soinsAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF