Intellectual disability and cancer susceptibility in a family with inherited 14q32.13q32.2 deletion.
JACQUINET, Adeline ; CABERG, Jean-Hubert ; BOURS, Vincent et al
Poster (2013, June)
Located in 14q32.13, DICER1 codes for an RNase III endoribonuclease essential in the processing of microRNAs. These microRNAs are functional non-coding RNAs that regulate gene expression at a post ... [more ▼]
Located in 14q32.13, DICER1 codes for an RNase III endoribonuclease essential in the processing of microRNAs. These microRNAs are functional non-coding RNAs that regulate gene expression at a post-transcriptional level by interfering with translation and degradation of target messenger RNAs. Their deregulations have been implicated in several human diseases and cancers. Germline mutations in DICER1 are associated with a low susceptibility risk to tumor development. Inactivating mutations have been identified in patients and families with various benign and malignant tumors, especially pleuropulmonary blastoma, cystic nephroma and ovarian Sertoli-Leydig tumors. Germline DICER1 deletion has not been reported so far. We report a 7-year-old girl with an inherited DICER1 deletion. She was referred for mild intellectual deficiency, a medical history of cystic nephroma and dysmorphic features. Her father, two paternal uncles and the paternal grandmother had mild to moderate intellectual disabilities. The deceased grandmother had presented uterin and ovarian tumors. Array-CGH analysis identified a 5041kb deletion in 14q32.13-q32.2 in the patient, the father, the two uncles and the paternal grandmother. The deletion contained 50 coding genes and led to DICER 1 haploinsufficiency which was responsible for cancer susceptibility. Moreover, transmission of the deletion was related to intellectual disability in this family. The 14q32.13q32.2 locus has been previously associated with autosomal recessive mental retardation, suggesting the presence in the region of genes implicated in cerebral development and cognitive functions. [less ▲]Detailed reference viewed: 14 (1 ULg)
Connectome-based classification of BDNF Met allele carriers
Ziegler, Erik ; ; Mascetti, Laura et al
Poster (2013, June)
Secretion of brain-derived neurotrophic factor (BDNF) is essential for synaptic plasticity in the central nervous system during neurodevelopment [Huang]. A common human non-synonymous SNIP in the BDNF ... [more ▼]
Secretion of brain-derived neurotrophic factor (BDNF) is essential for synaptic plasticity in the central nervous system during neurodevelopment [Huang]. A common human non-synonymous SNIP in the BDNF gene (Val66Met, rs6265) decreases activity-dependent BDNF release in neurons transfected with the human A allele (Met-BDNF). We reasoned that the persistent differential activity-dependent BDNF release implied by this polymorphism should also be associated with differences in adult brain structure. The study population comprised 36 healthy subjects (aged 18-25): 15 (9 male) were identified as carrying the Met allele (“Met carrier” group) and 21 (9 male) were homozygotes for the Val allele (“Val/Val” group). The groups did not vary significantly in IQ, age nor scores for a battery of psychological tests. A high-resolution T1-weighted image (sMRI), 7 unweighted (b=0) and a set of diffusion-weighted (b=1000) images using 61 non-collinear directional gradients were acquired for each subject. The processing workflow relied on several pieces of software and was developed in Python and Nipype. The sMRIs were segmented using the automated labeling of Freesurfer [Desikan] and further parcellated using the Lausanne2008 atlas into 1015 regions of interest (ROIs) [Cammoun]. DWIs were corrected for image distortions (due to eddy currents) using linear coregistration functions from FSL [Smith]. Fractional anisotropy maps were generated, and a few single-fiber (high FA) voxels were used to estimate the spherical harmonic coefficients (order 8) of the response function from the DWIs [Tournier]. Then orientation distribution functions were obtained at each voxel. Probabilistic tractography was performed throughout the whole brain using seeds from subject-specific white-matter masks and a predefined number of tracts (300,000), see Fig. 1. The tracks were affine-transformed into the subject's structural space with Dipy [Garyfallidis]. Connectome mapping was performed by considering every contact point between each tract and the outlined ROIs (unlike in [Hagmann]): the connectivity matrix was incremented every time a single fiber traversed between any two ROIs. We trained a Gaussian Process Classifier [Rasmussen] (interfaced by PRoNTo [Schrouff]) on these connectivity matrices. The accuracy and generalization ability of the classification were assessed with a leave-one-subject-out cross-validation procedure. With this linear kernel method weights were also obtained indicating the contribution to the classification output (in favor of either genotypic group) of each edge in the network. The same method was employed to discriminate features related to the subjects' gender and genotype for the ADA gene. The classifier was able to discriminate between Val/Val and Met carriers with 86.1% balanced accuracy. The predictive value for the Val/Val and Met carrier groups were 94.4% (p=0.001) and 77.8% (p=0.003), respectively. In Fig. 2 the weights obtained by the classifier are visualized as edges in the brain network. For the classifier trained to identify gender or the subjects' ADA genotype, the global accuracy reached 63.9% (n.s.) and 58.3% (n.s.) respectively. Using high-resolution connectome mapping from normal young healthy human volunteers grouped based on the Met allele of the BNDF gene, we show that the BDNF genotype of an individual can be significantly identified from his structural brain wiring. These differences appear specific to this allele; no such difference could be found for the polymorphism in the ADA gene, or even for gender. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in Met carriers, and that this produces mesoscale changes in white matter architecture. Acknowledgements: the FNRS, the ULg, the Queen Elisabeth Medical Foundation, the Léon Fredericq Foundation, the Belgian Inter-University Attraction Program, the Welbio program, and the MCITN in Neurophysics (PITN-GA-2009-238593). Cammoun L. et al. (2011), ‘Mapping the human connectome at multiple scales with diffusion spectrum MRI’, J Neuroscience Methods, 203:386–397. Desikan R.S. et al. (2006), ‘An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest’, Neuroimage, 31:968-980. Hagmann P. et al. (2008), ‘Mapping the structural core of human cerebral cortex’, PLoS Biology, 6:e159 Huang E.J., Reichardt L.F. (2001), ‘Neurotrophins: roles in neuronal development and function’, Annual Review of Neuroscience, 24:677-736. Garyfallidis E. et al. (2011), ‘Dipy - a novel software library for diffusion MR and tractography’, 17th Annual Meeting of the Organization for Human Brain Mapping. http://nipy.sourceforge.net/dipy/ Rasmussen C.E. (2006), Gaussian processes for machine learning. Schrouff J. et al. (2012), ‘PRoNTo: Pattern Recognition for Neuroimaging Toolbox’, 18th Annual Meeting of the Organization for Human Brain Mapping. http://www.mlnl.cs.ucl.ac.uk/pronto Smith S.M. et al. (2004), ‘Advances in functional and structural MR image analysis and implementation as FSL’, Neuroimage, 23 Suppl 1:S208-S219. Tournier J.D., et al. (2007), ‘Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution’, Neuroimage, 35:1459-1472. [less ▲]Detailed reference viewed: 120 (17 ULg)
Exome sequencing of tumors: relevance in copy-number alteration (CNA) analysis and fixed tissue samples.
Wenric, Stéphane ; JOSSE, Claire ; Fasquelle, Corinne et al
Poster (2013, March 15)
Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 ... [more ▼]
Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 forms, as well as SNP and CNA detection. A comparison of the various metrics and results related to the sequencing, mapping, and variants detection has been done, outlining what can, and can’t be done with exome data sequenced from cryopreserved and FFPE tissue. [less ▲]Detailed reference viewed: 26 (6 ULg)
Clinical, cytogenetic and molecular characterization of two cases of mosaic ring chromosome 13.
Uwineza, Annette ; PIERQUIN, Geneviève ; GAILLEZ, Stephanie et al
in Genetic counseling (Geneva, Switzerland) (2013), 24(2), 193-200
The occurrence of mosaic ring chromosome 13 is rare. The mechanism of ring chromosome formation is usually associated with loss of genetic material. We report 2 cases of mosaic ring chromosome 13 ... [more ▼]
The occurrence of mosaic ring chromosome 13 is rare. The mechanism of ring chromosome formation is usually associated with loss of genetic material. We report 2 cases of mosaic ring chromosome 13, resulting in deletion of 13qter. The first patient, a 15 year-old boy, presented a delayed psychomotor development, mental retardation, dysmorphic features and bleeding disorders associated with a de novo terminal 13q34 deletion. The second case was a foetus of 31 weeks with prenatal diagnosis of severe malformation such as holoprosencephaly, congenital cardiac defects, gastro-intestinal abnormalities with intrauterine growth retardation, the molecular analysis showed a de novo deletion encompassing the region 13q31.3-q34. [less ▲]Detailed reference viewed: 81 (10 ULg)
Genetic diagnosis of Duchenne and Becker muscular dystrophy using multiplex ligation-dependent probe amplification in Rwandan patients.
Uwineza, Annette ; ; et al
in Journal of tropical pediatrics (2013)
Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic ... [more ▼]
Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic diagnosis was carried out in six Rwandan patients presenting a phenotype of Duchenne and Becker muscular dystrophies and six asymptomatic female carrier relatives using multiplex ligation-dependent probe amplification (MLPA). Our results revealed deletion of the exons 48-51 in one patient, an inherited deletion of the exons 8-21 in two brothers and a de novo deletion of the exons 46-50 in the fourth patient. No copy number variation was found in two patients. Only one female carrier presented exon deletion in the DMD gene. This is the first cohort of genetic analysis in Rwandan patients affected by Duchenne and Becker muscular dystrophies. This report confirmed that MLPA assay can be easily implemented in low-income countries. [less ▲]Detailed reference viewed: 48 (18 ULg)
Existe-t-il une predisposition genetique aux addictions ?
CASTERMANS, Emilie ; GAILLEZ, Stephanie ; BOURS, Vincent
in Revue Médicale de Liège (2013), 68(5-6), 226-32
Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased ... [more ▼]
Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased? Addiction predisposition is a complex trait, involving numerous predisposition genes and also environment. Heritability of this trait is 50%, meaning a similar contribution of genes and environment in the setting of this trait. Some genes of the dopaminergic system and some others specific for various drugs metabolism have been associated to addictions. The growth of those findings into promising pilot treatments seems a good future coming in. [less ▲]Detailed reference viewed: 120 (10 ULg)
Concurrent Synaptic and Systems Memory Consolidation during Sleep
; ; Schrouff, Jessica et al
in Journal of Neuroscience (2013), 33(24), 10182-10190
Memories are consolidated during sleep by two apparently antagonistic processes: (1) reinforcement of memory-specific cortical interactions and (2) homeostatic reduction in synaptic efficiency. Using fMRI ... [more ▼]
Memories are consolidated during sleep by two apparently antagonistic processes: (1) reinforcement of memory-specific cortical interactions and (2) homeostatic reduction in synaptic efficiency. Using fMRI, we assessed whether episodic memories are processed during sleep by either or both mechanisms, by comparing recollection before and after sleep. We probed whether LTP influences these processes by contrasting two groups of individuals prospectively recruited based on BDNF rs6265 (Val66Met) polymorphism. Between immediate retrieval and delayed testing scheduled after sleep, responses to recollection increased significantly more in Val/Val individuals than in Met carriers in parietal and occipital areas not previously engaged in retrieval, consistent with “systems-level consolidation.” Responses also increased differentially between allelic groups in regions already activated before sleep but only in proportion to slow oscillation power, in keeping with “synaptic downscaling.” Episodic memories seem processed at both synaptic and systemic levels during sleep by mechanisms involving LTP. [less ▲]Detailed reference viewed: 31 (5 ULg)
In Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow
Wislet, Sabine ; Poulet, Christophe ; Neirinckx, Virginie et al
in PLoS ONE (2012), 7(10), 46425
Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells ... [more ▼]
Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. [less ▲]Detailed reference viewed: 34 (10 ULg)
Overexpression of CD39 in mouse airways promotes bacteria induced inflammation
Theatre, Emilie ; ; et al
in Journal of Immunology (2012), 189(4), 1966-1974
In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of ... [more ▼]
In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases.We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8+ T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X1 or P2X7 receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation. [less ▲]Detailed reference viewed: 57 (11 ULg)
Maladies complexes: des interactions genes-environnement au probleme de sante publique.
SCHEEN, André ; Bours, Vincent
in Revue Médicale de Liège (2012), 67(5-6), 217-9Detailed reference viewed: 52 (3 ULg)
A new 48, XXYY/47, XYY syndrome associated with multiple skeletal abnormalities, congenital heart disease and mental retardation.
; JAMAR, Mauricette ; PIERQUIN, Geneviève et al
in Indian journal of human genetics (2012), 18(3), 352-5
While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present ... [more ▼]
While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present observation, a boy with congenital scoliosis due to segmented thoracic hemivertebra associated with radioulnar synostosis and congenital heart disease is described. Chromosome G-banding and FISH analysis demonstrated a de novo mosaic karyotype 48, XXYY/47, XYY in this patient. To the best of our knowledge, this is the first report of a combination of XYY and XXYY syndromes. [less ▲]Detailed reference viewed: 44 (2 ULg)
Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells.
KROONEN, Jérôme ; Artesi, Maria ; CAPRARO, Valérie et al
in International Journal of Oncology (2012), 41(2), 776-82
Inhibitors of casein kinase 2 (CK2), a regulator of cell proliferation and mediator of the DNA damage response, are being evaluated in clinical trials for the treatment of cancers. Apigenin was capable of ... [more ▼]
Inhibitors of casein kinase 2 (CK2), a regulator of cell proliferation and mediator of the DNA damage response, are being evaluated in clinical trials for the treatment of cancers. Apigenin was capable of inhibiting the activation of CK2 following gamma irradiation in LN18 and U87 malignant glioma cells. Apigenin and siRNA-mediated CK2 protein depletion further inhibited NF-kappaB activation and altered the Tyr68 phosphorylation of Chk2 kinase, a DNA damage response checkpoint kinase, following irradiation. However, CK2 inhibition did not decrease the ability of these glioma cells to repair double-strand DNA breaks, as assessed by COMET assays and gamma-H2Ax staining. Likewise, apigenin and siRNA-induced depletion of CK2 failed to sensitize glioma cells to the cytotoxic effect of 2 to 10 G-rays of gamma irradiation, as assessed by clonogenic assays. These results contrast with those found in other cancer types, and urge to prudence regarding the inclusion of malignant glioma patients in clinical trials that assess the radiosensitizing role of CK2 inhibitors in solid cancers. [less ▲]Detailed reference viewed: 24 (8 ULg)
Cyclin dependent kinase inhibitor (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenomas (FIPA) kindreds
; ; et al
in Endocrine-Related Cancer (2012), 19Detailed reference viewed: 14 (6 ULg)
Evidence of association between interferon regulatory factor 5 gene polymorphisms and asthma.
; ; et al
in Gene (2012), 504(2), 220-5
Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of ... [more ▼]
Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of interferon regulatory factor 5 (IRF5) in innate and adaptive immunity, we investigated the preferential transmission patterns of ten IRF5 gene polymorphisms in two asthmatic family cohorts. A common IRF5 haplotype was found to be associated with asthma and the severity of asthmatic symptoms. Stratified analysis of subgroups of asthmatic individuals revealed that the associations were more pronounced in nonatopic asthmatic individuals. In addition, the risk alleles of IRF5 polymorphisms for asthma were almost completely opposite to those for autoimmune disorders. Our study provides the first evidence of association between IRF5 and asthma, and sheds light on the related but potentially distinct roles of IRF5 alleles in the pathogenesis of asthma and autoimmune disorders. [less ▲]Detailed reference viewed: 34 (3 ULg)
Les maladies complexes: l'importance de la genetique.
LIBIOULLE, Cécile ; BOURS, Vincent
in Revue Médicale de Liège (2012), 67(5-6), 220-5
Complex diseases usually harbour hereditary factors linked with multiple susceptibility genes. The additive effects of genetic and environmental factors are responsible for the pathology. The impact of ... [more ▼]
Complex diseases usually harbour hereditary factors linked with multiple susceptibility genes. The additive effects of genetic and environmental factors are responsible for the pathology. The impact of heredity has been demonstrated through family studies, but also, and mostly, through the study of adopted people and twins. Recently, genome wide association studies (GWAS) allowed the identification of many susceptibility genes for most complex diseases. However, a large part of the heritability is still missing, probably because of insufficient exploration of rare genetic variants and/or epigenetic factors. The ultimate goal of these genetic studies is the definition of an individual risk leading to specific preventive measures (model "predict and prevent"), but this purpose remains very remote for the majority of complex diseases. [less ▲]Detailed reference viewed: 121 (6 ULg)
ATP-gated P2X1 ion channels protect from endotoxemia by dampening neutrophil activation
Lecut, Christelle ; Faccinetto, Céline ; Delierneux, Céline et al
in Journal of Thrombosis and Haemostasis [=JTH] (2012), 10(3), 453-65
Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to ... [more ▼]
Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X1 ion channels are involved in promoting neutrophil chemotaxis. <br />Objectives: To elucidate the contribution of P2X1 ion channels to sepsis and associated disturbance of hemostasis. <br />Methods: We used P2X1-/- mice in a model of lipopolysaccharide (LPS)-induced sepsis. Hemostasis and inflammation parameters were analysed together with outcome. Mechanisms were further studied ex vivo using mouse and human blood or isolated neutrophils and monocytes. <br />Results: P2X1-/- mice were more susceptible to LPS-induced shock than wild-type mice despite normal cytokine production. Plasma levels of thrombin-antithrombin complexes were higher, thrombocytopenia was worsened and whole blood coagulation time was markedly reduced, pointing to aggravated hemostasis disturbance in the absence of P2X1. However, whole blood platelet aggregation occurred normally and P2X1-/- macrophages displayed normal levels of total tissue factor activity. We found that P2X1-/- neutrophils produced higher amounts of reactive oxygen species. Increased amounts of myeloperoxidase were released in the blood of LPS-treated P2X1-/- mice, and circulating neutrophils and monocytes expressed higher levels of CD11b. Neutrophil accumulation into the lungs was also significantly augmented, as was lipid peroxidation in the liver. Desensitization of P2X1 ion channels led to increased activation of human neutrophils and enhanced formation of platelet-leukocyte aggregates. [less ▲]Detailed reference viewed: 50 (20 ULg)
Partial trisomy 4q associated with young-onset dopa-responsive parkinsonism.
Garraux, Gaëtan ; CABERG, Jean-Hubert ; et al
in Archives of Neurology (2012), 69(3), 398-400
OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder ... [more ▼]
OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder Outpatient Clinic at the University Hospital Centre, Liege, Belgium. Patient A 31-year-old woman. MAIN OUTCOME MEASURES: Clinical, neuroimaging, and genetic data. RESULTS: The duplicated region contains 150 known genes, including the alpha-synuclein (SNCA) gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography features are similar to those previously reported in heterozygote SNCA duplication carriers. Altered expression of other genes contained in the duplicated region may contribute to clinical features that are uncommon in the phenotypic spectrum of SNCA multiplications such as delayed developmental psychomotor milestones during infancy and musculoskeletal abnormalities. CONCLUSION: This case report provides new insights on the genetic basis of parkinsonism. [less ▲]Detailed reference viewed: 42 (11 ULg)
Co-Occurence of two rare autosomal recessive syndromes in a young patient
SEGERS, Karin ; Debray, François-Guillaume ; et al
Poster (2011, March 04)Detailed reference viewed: 10 (4 ULg)
Genetic screening for AIP mutations in Young patients with sporadic and Familial Pituitary Macroadenomas
; ; Daly, Adrian et al
in Endocrinologia = Endokrinologiia (2011), 16(1), 41-48Detailed reference viewed: 28 (12 ULg)
Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection.
Kroonen, Jérôme ; Nassen, Jessica ; et al
in International Journal of Cancer = Journal International du Cancer (2011), 129(3), 574-585
This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs ... [more ▼]
This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs following xenograft in the caudate putamen of immunodeficient mice.In patients with glioblastoma multiforme, recurrence is the rule despite continuous advances in surgery, radiotherapy and chemotherapy. Within these malignant gliomas, glioblastoma stem cells or initiating cells have been recently described and they were shown to be specifically involved in experimental tumorigenesis. In this study, we show that some human glioblastoma cells injected into the striatum of immunodeficient nude mice exhibit a tropism for the subventricular zones. There and similarily to neurogenic stem cells, these subventricular glioblastoma cells were then able to migrate towards the olfactory bulbs. Finally, the glioblastoma cells isolated from the adult mouse subventricular zones and olfactory bulbs display high tumorigenicity when secondary injected in a new mouse brain. Together, these data suggest that neurogenic zones could be a reservoir for particular cancer-initiating cells. [less ▲]Detailed reference viewed: 81 (35 ULg)