French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

Abstract: Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.

Brain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study.

Abstract: The neurophysiological mechanisms underlying mismatch negativity (MMN) can be inferred from an examination of some of the brain generators involved in the process of this event-related potential (ERP) component. ERPs were recorded in two studies in which the subjects were involved in a selective dichotic listening task. Subjects were required to silently count rare stimuli deviating in pitch from a sequence of standard stimuli in one ear, while ignoring all the stimuli (standards and deviants) delivered randomly to the other ear. The results showed that, in all cases, the negative wave elicited by the deviant stimuli showed the highest amplitudes over the right hemiscalp irrespective of the ear of stimulation or the direction of attention. Scalp radial current density analysis showed that this asymmetric potential distribution could be attributed to the sum of activities of two sets of neural generators: one temporal, located in the vicinity of the primary auditory cortex, predominantly activated in the hemisphere contralateral to the ear of stimulation, and the other frontal, involving mainly the right hemisphere. The results are discussed in light of Naatanen's model: we suggest the dissociation of two functional processes on the basis of activity of distinct brain areas: a sensory memory mechanism related to the temporal generators, and an automatic attention-switching process related to the frontal generators.

Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts

Abstract: Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.

CluePedia Cytoscape plugin

Abstract: Summary: The CluePedia Cytoscape plugin is a search tool for new markers potentially associated to pathways. CluePedia calculates linear and non-linear statistical dependencies from experimental data. Genes, proteins and miRNAs can be connected based on in silico and/or experimental information and integrated into a ClueGO network of terms/pathways. Interrelations within each pathway can be investigated, and new potential associations may be revealed through gene/protein/miRNA enrichments. A pathway-like visualization can be created using the Cerebral plugin layout. Combining all these features is essential for data interpretation and the generation of new hypotheses. The CluePedia Cytoscape plugin is user-friendly and has an expressive and intuitive visualization. Availability: http://www.ici.upmc.fr/cluepedia/ and via the Cytoscape plugin manager. The user manual is available at the CluePedia website. Contact: bernhard.mlecnik@crc.jussieu.fr or jerome.galon@crc.jussieu.fr Supplementary information:Supplementary data are available at Bioinformatics online.