24 results on '"Gaillard JB"'
Search Results
2. Effective requesting method to detect fusion transcripts in chronic myelomonocytic leukemia RNA-seq.
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Rufflé F, Reboul J, Boureux A, Guibert B, Bessière C, Silva R, Jourdan E, Gaillard JB, Boland A, Deleuze JF, Sénamaud-Beaufort C, Selimoglu-Buet D, Solary E, Gilbert N, and Commes T
- Abstract
RNA sequencing technology combining short read and long read analysis can be used to detect chimeric RNAs in malignant cells. Here, we propose an integrated approach that uses k-mers to analyze indexed datasets. This approach is used to identify chimeric RNA in chronic myelomonocytic leukemia (CMML) cells, a myeloid malignancy that associates features of myelodysplastic and myeloproliferative neoplasms. In virtually every CMML patient, new generation sequencing identifies one or several somatic driver mutations, typically affecting epigenetic, splicing and signaling genes. In contrast, cytogenetic aberrations are currently detected in only one third of the cases. Nevertheless, chromosomal abnormalities contribute to patient stratification, some of them being associated with higher risk of poor outcome, e.g. through transformation into acute myeloid leukemia (AML). Our approach selects four chimeric RNAs that have been detected and validated in CMML cells. We further focus on NRIP1-MIR99AHG , as this fusion has also recently been detected in AML cells. We show that this fusion encodes three isoforms, including a novel one. Further studies will decipher the biological significance of such a fusion and its potential to improve disease stratification. Taken together, this report demonstrates the ability of a large-scale approach to detect chimeric RNAs in cancer cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
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- 2024
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3. Cytogenetics in the management of hematological malignancies: An overview of alternative technologies for cytogenetic characterization.
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Lestringant V, Guermouche-Flament H, Jimenez-Pocquet M, Gaillard JB, and Penther D
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- Humans, DNA Copy Number Variations, Chromosome Aberrations, Cytogenetics methods, Genomics methods, Hematologic Neoplasms genetics, Hematologic Neoplasms diagnosis, Hematologic Neoplasms therapy, Cytogenetic Analysis methods
- Abstract
Genomic characterization is an essential part of the clinical management of hematological malignancies for diagnostic, prognostic and therapeutic purposes. Although CBA and FISH are still the gold standard in hematology for the detection of CNA and SV, some alternative technologies are intended to complement their deficiencies or even replace them in the more or less near future. In this article, we provide a technological overview of these alternatives. CMA is the historical and well established technique for the high-resolution detection of CNA. For SV detection, there are emerging techniques based on the study of chromatin conformation and more established ones such as RTMLPA for the detection of fusion transcripts and RNA-seq to reveal the molecular consequences of SV. Comprehensive techniques that detect both CNA and SV are the most interesting because they provide all the information in a single examination. Among these, OGM is a promising emerging higher-solution technique that offers a complete solution at a contained cost, at the expense of a relatively low throughput per machine. WGS remains the most adaptable solution, with long-read approaches enabling very high-resolution detection of CAs, but requiring a heavy bioinformatics installation and at a still high cost. However, the development of high-resolution genome-wide detection techniques for CAs allows for a much better description of chromoanagenesis. Therefore, we have included in this review an update on the various existing mechanisms and their consequences and implications, especially prognostic, in hematological malignancies., Competing Interests: Declaration of competing interest The authors declare no Conflict of Interest., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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4. Molecular landscape of mature B-cell lymphoproliferative disorders with BCL3-translocation: A Groupe Francophone de Cytogénétique Hématologique (GFCH)/French Innovative Leukemia Organization (FILO) study.
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Véronèse L, Bensaber H, Dannus LT, Giannone G, Choiset C, Grimpret C, Abermil N, Balducci E, Bidet A, Chapiro E, Couronné L, Daudignon A, Douet-Gilbert N, Eclache V, Gaillard B, Gaillard JB, Hsoumi F, Lefebvre C, Nadal N, Mozziconacci MJ, Penther D, Ribourtout B, Richebourg S, Rigollet L, Terre C, Soler G, Tournilhac O, Guièze R, Nguyen-Khac F, and Tchirkov A
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- Humans, Male, Female, Middle Aged, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders diagnosis, Aged, B-Lymphocytes metabolism, B-Lymphocytes pathology, Adult, France, B-Cell Lymphoma 3 Protein, Translocation, Genetic
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- 2024
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5. Cytogenetics in the management of mature B-cell non-Hodgkin lymphomas: Guidelines from the Groupe Francophone de Cytogénétique Hematologique (GFCH).
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Lefebvre C, Veronese L, Nadal N, Gaillard JB, Penther D, Daudignon A, Chauzeix J, Nguyen-Khac F, and Chapiro E
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- Adult, Humans, Chromosome Aberrations, Cytogenetic Analysis, In Situ Hybridization, Fluorescence, Proto-Oncogene Proteins c-bcl-2 genetics, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Non-Hodgkin genetics, Lymphoma, Non-Hodgkin therapy
- Abstract
Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas., (Copyright © 2023. Published by Elsevier Masson SAS.)
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- 2023
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6. Cytogenetics in the management of mature T-cell and NK-cell neoplasms: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).
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Gaillard JB, Chapiro E, Daudignon A, Nadal N, Penther D, Chauzeix J, Nguyen-Khac F, Veronese L, and Lefebvre C
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- Humans, Cytogenetic Analysis methods, Killer Cells, Natural, T-Lymphocytes, Hematology, Lymphoma
- Abstract
Mature T-cell and natural killer (NK)-cell neoplasms (MTNKNs) are a highly heterogeneous group of lymphomas that represent 10-15 % of lymphoid neoplasms and have usually an aggressive behavior. Diagnosis can be challenging due to their overlapping clinical, histological and immunophenotypic features. Genetic data are not a routine component of the diagnostic algorithm for most MTNKNs. Indeed, unlike B-cell lymphomas, the genomic landscape of MTNKNs is not fully understood. Only few characteristic rearrangements can be easily identified with conventional cytogenetic methods and are an integral part of the diagnostic criteria, for instance the t(14;14)/inv(14) or t(X;14) abnormality harbored by 95 % of patients with T-cell prolymphocytic leukemia, or the ALK gene translocation observed in some forms of anaplastic large cell lymphoma. However, advances in molecular and cytogenetic techniques have brought new insights into MTNKN pathogenesis. Several recurrent genetic alterations have been identified, such as chromosomal losses involving tumor suppressor genes (SETD2, CDKN2A, TP53) and gains involving oncogenes (MYC), activating mutations in signaling pathways (JAK-STAT, RAS), and epigenetic dysregulation, that have improved our understanding of these pathologies. This work provides an overview of the cytogenetics knowledge in MTNKNs in the context of the new World Health Organization classification and the International Consensus Classification of hematolymphoid tumors. It describes key genetic alterations and their clinical implications. It also proposes recommendations on cytogenetic methods for MTNKN diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
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- 2023
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7. Antenatal ultrasound features of isolated recurrent copy number variation in 7q11.23 (Williams syndrome and 7q11.23 duplication syndrome).
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Courdier C, Boudjarane J, Malan V, Muti C, Sperelakis-Beedham B, Odent S, Jaillard S, Quelin C, Le Caignec C, Patat O, Dubucs C, Julia S, Schluth-Bolard C, Goumy C, Redon S, Gaillard JB, Huynh MT, Dupont C, Tabet AC, Cogan G, Vialard F, Dard R, Jedraszak G, Jobic F, Lefebvre M, Quenum G, Inai S, Rama M, Sauvestre F, Coatleven F, Thomas J, and Rooryck C
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- Humans, Female, Pregnancy, DNA Copy Number Variations, Retrospective Studies, Fetal Growth Retardation, Ultrasonography, Williams Syndrome diagnostic imaging, Williams Syndrome genetics, Williams Syndrome complications
- Abstract
Objective: We aimed to gather fetal cases carrying a 7q11.23 copy number variation (CNV) and collect precise clinical data to broaden knowledge of antenatal features in these syndromes., Methods: We retrospectively recruited unrelated cases with 7q11.23 deletion, known as Williams-Beuren syndrome (WBS), or 7q11.23 duplication who had prenatal ultrasound findings. We collected laboratory and clinical data, fetal ultrasound, cardiac ultrasound and fetal autopsy reports from 18 prenatal diagnostic centers throughout France., Results: 40 fetuses with WBS were collected and the most common features were intra-uterine growth retardation (IUGR) (70.0%, 28/40), cardiovascular defects (30.0%, 12/40), polyhydramnios (17.5%, 7/40) and protruding tongue (15.0%, 6/40). Fetal autopsy reports were available for 11 cases and were compared with ultrasound prenatal features. Four cases of fetuses with 7q11.23 microduplication were collected and prenatal ultrasound signs were variable and often isolated., Conclusion: This work strengthens the fact that 7q11.23 CNVs are associated with a broad spectrum of antenatal presentations. IUGR and cardiovascular defects were the most frequent ultrasound signs. By reporting the biggest series of antenatal WBS, we aim to better delineate distinctive signs in fetuses with 7q11.23 CNVs., (© 2023 John Wiley & Sons Ltd.)
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- 2023
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8. Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in east occitania.
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Robin JB, Theron A, Quittet P, Exbrayat C, Gaillard JB, Lavabre-Bertrand T, David S, Saad A, Jourdan E, and Cartron G
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- Humans, Protein Kinase Inhibitors adverse effects, Recurrence, Retrospective Studies, Leukemia, Myelogenous, Chronic, BCR-ABL Positive chemically induced, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Leukemia, Myeloid, Chronic-Phase
- Abstract
Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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9. AnnotSV and knotAnnotSV: a web server for human structural variations annotations, ranking and analysis.
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Geoffroy V, Guignard T, Kress A, Gaillard JB, Solli-Nowlan T, Schalk A, Gatinois V, Dollfus H, Scheidecker S, and Muller J
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- Genome, Human, Genomics, Humans, Internet, Molecular Sequence Annotation, Phenotype, Polymorphism, Single Nucleotide, Genomic Structural Variation, Software
- Abstract
With the dramatic increase of pangenomic analysis, Human geneticists have generated large amount of genomic data including millions of small variants (SNV/indel) but also thousands of structural variations (SV) mainly from next-generation sequencing and array-based techniques. While the identification of the complete SV repertoire of a patient is getting possible, the interpretation of each SV remains challenging. To help identifying human pathogenic SV, we have developed a web server dedicated to their annotation and ranking (AnnotSV) as well as their visualization and interpretation (knotAnnotSV) freely available at the following address: https://www.lbgi.fr/AnnotSV/. A large amount of annotations from >20 sources is integrated in our web server including among others genes, haploinsufficiency, triplosensitivity, regulatory elements, known pathogenic or benign genomic regions, phenotypic data. An ACMG/ClinGen compliant prioritization module allows the scoring and the ranking of SV into 5 SV classes from pathogenic to benign. Finally, the visualization interface displays the annotated SV in an interactive way including popups, search fields, filtering options, advanced colouring to highlight pathogenic SV and hyperlinks to the UCSC genome browser or other public databases. This web server is designed for diagnostic and research analysis by providing important resources to the user., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2021
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10. 12/111phiA Prophage Domestication Is Associated with Autoaggregation and Increased Ability to Produce Biofilm in Streptococcus agalactiae .
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Renard A, Diene SM, Courtier-Martinez L, Gaillard JB, Gbaguidi-Haore H, Mereghetti L, Quentin R, Francois P, and Van Der Mee-Marquet N
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CC17 Streptococcus agalactiae carrying group-A prophages is increasingly responsible for neonatal infections. To investigate the impact of the genetic features of a group-A prophage, we first conducted an in silico analysis of the genome of 12/111phiA, a group-A prophage carried by a strain responsible for a bloodstream infection in a parturient. This revealed a Restriction Modification system, suggesting a prophage maintenance strategy and five ORFs of interest for the host and encoding a type II toxin antitoxin system RelB/YafQ, an endonuclease, an S-adenosylmethionine synthetase MetK, and an StrP-like adhesin. Using the WT strain cured from 12/111phiA and constructing deleted mutants for the ORFs of interest, and their complemented mutants, we demonstrated an impact of prophage features on growth characteristics, cell morphology and biofilm formation. Our findings argue in favor of 12/111phiA domestication by the host and a role of prophage features in cell autoaggregation, glycocalyx and biofilm formation. We suggest that lysogeny may promote GBS adaptation to the acid environment of the vagina, consequently colonizing and infecting neonates.
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- 2021
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11. Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities.
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Gailllard B, Cornillet-Lefebvre P, Le QH, Maloum K, Pannetier M, Lecoq-Lafon C, Grange B, Jondreville L, Michaux L, Nadal N, Ittel A, Luquet I, Struski S, Lefebvre C, Gaillard JB, Lafage-Pochitaloff M, Balducci E, Penther D, Barin C, Collonge-Rame MA, Jimenez-Poquet M, Richebourg S, Lemaire P, Defasque S, Radford-Weiss I, Bidet A, Susin SA, Nguyen-Khac F, and Chapiro E
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- Adult, Aged, Aged, 80 and over, Bronchial Neoplasms diagnosis, Bronchial Neoplasms metabolism, Cell Differentiation, Chromosome Aberrations, Female, Genes, p53 genetics, Humans, Immunoglobulin Heavy Chains metabolism, In Situ Hybridization, Fluorescence methods, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, B-Cell, Marginal Zone diagnosis, Lymphoma, B-Cell, Marginal Zone drug therapy, Male, Middle Aged, Mutation, Phenotype, Survival Analysis, Tertiary Lymphoid Structures pathology, Translocation, Genetic genetics, Trisomy genetics, CD5 Antigens metabolism, Cyclin-Dependent Kinase 6 metabolism, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Lymphoma, B-Cell, Marginal Zone metabolism, Splenic Neoplasms pathology, Tumor Suppressor Protein p53 metabolism
- Abstract
A translocation involving the cyclin-dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B-cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T-cell receptor alpha locus (TRA)/T-cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B-cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B-cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus-associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy-chain variable-region (IGHV) locus sequencing revealed that none harboured an IGHV1-02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B-cell lymphomas with distinctive features., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2021
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12. Mosaic complete tetrasomy 21 in a fetus with complete atrioventricular septal defect and minor morphological variations.
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Gatinois V, Bigi N, Mousty E, Chiesa J, Musizzano Y, Schneider A, Lefort G, Pinson L, Gaillard JB, Ragon C, Perez MJ, Tournaire M, Blanchet P, Corsini C, Haquet E, Callier P, Geneviève D, Pellestor F, and Puechberty J
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- Adult, Amniocentesis, Female, Heart Septal Defects genetics, Humans, Pregnancy, Aneuploidy, Chromosomes, Human, Pair 21 genetics, Heart Septal Defects diagnosis, Mosaicism, Prenatal Diagnosis methods, Tetrasomy
- Abstract
Background: Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well-documented description of a complete tetrasomy 21 in the literature., Methods: Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21., Results: Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21)., Conclusion: Our observation and the review of the literature reported the possibility of very weak mosaicism and disease-causing confined tissue-specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false-negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
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- 2019
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13. Disruption of chromatin organisation causes MEF2C gene overexpression in intellectual disability: a case report.
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Yauy K, Schneider A, Ng BL, Gaillard JB, Sati S, Coubes C, Wells C, Tournaire M, Guignard T, Bouret P, Geneviève D, Puechberty J, Pellestor F, and Gatinois V
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- Child, Child, Preschool, Chromosome Banding, Chromosomes, Human, Pair 3 genetics, Chromosomes, Human, Pair 5 genetics, Female, Gene Duplication, Humans, Infant, Infant, Newborn, MEF2 Transcription Factors genetics, Chromatin metabolism, Intellectual Disability genetics
- Abstract
Background: Balanced structural variants are mostly described in disease with gene disruption or subtle rearrangement at breakpoints., Case Presentation: Here we report a patient with mild intellectual deficiency who carries a de novo balanced translocation t(3;5). Breakpoints were fully explored by microarray, Array Painting and Sanger sequencing. No gene disruption was found but the chromosome 5 breakpoint was localized 228-kb upstream of the MEF2C gene. The predicted Topologically Associated Domains analysis shows that it contains only the MEF2C gene and a long non-coding RNA LINC01226. RNA studies looking for MEF2C gene expression revealed an overexpression of MEF2C in the lymphoblastoid cell line of the patient., Conclusions: Pathogenicity of MEF2C overexpression is still unclear as only four patients with mild intellectual deficiency carrying 5q14.3 microduplications containing MEF2C are described in the literature. The microduplications in these individuals also contain other genes expressed in the brain. The patient presented the same phenotype as 5q14.3 microduplication patients. We report the first case of a balanced translocation leading to an overexpression of MEF2C similar to a functional duplication.
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- 2019
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14. Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia.
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Bidet A, Dulucq S, Smol T, Marceau-Renaut A, Morisset S, Coiteux V, Noël-Walter MP, Nicolini FE, Tigaud I, Luquet I, Struski S, Gaillard B, Penther D, Tondeur S, Nadal N, Hermet E, Véronèse L, Réa D, Gervais C, Theisen O, Terré C, Cony-Makhoul P, Lefebvre C, Gaillard JB, Radford I, Vervaeke AL, Barin C, Chapiro E, Nguyen-Khac F, Etienne G, Preudhomme C, Mahon FX, and Roche-Lestienne C
- Subjects
- Alleles, Chromosome Deletion, Disease Progression, Female, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Prognosis, Survival Analysis, Chromosome Aberrations, Chromosomes, Human, Pair 7, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive etiology, Metaphase genetics, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics
- Abstract
Clonal chromosome abnormalities in Philadelphia-negative cells could concern chronic myeloid leukemia patients treated by tyrosine kinase inhibitors. The European LeukemiaNet distinguishes -7/del(7q) abnormalities as a "warning". However, the impact of clonal chromosome abnormalities, and specifically those of -7/del(7q), in Philadelphia-negative cells on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome. The aim of this study was to determine whether the impact of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells on the clinical outcome is different from that of other types of abnormalities, and we argue for an underlying associated high-risk myelodysplastic syndrome. Among 102 chronic myeloid leukemia patients with clonal chromosome abnormalities in Philadelphia-negative cells with more than a median of 6 years of follow up, patients with -7/del(7q) more frequently had signs of dysplasia, a lower cumulative incidence of deep molecular response and often needed further treatment lines, with the consequent impact on event-free and progression-free survival. Morphological features of dysplasia are associated with myelodysplastic syndrome/acute myeloid leukemia mutations and compromise the optimal response to tyrosine kinase inhibitors, irrespectively of the type of clonal chromosome abnormalities in Philadelphia-negative cells. However, mutation patterns determined by next-generation sequencing could not clearly explain the underlying high-risk disease. We hereby confirm the pejorative prognostic value of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells and suggest that myelodysplastic features constitute a warning signal that response to tyrosine kinase inhibitors may be less than optimal., (Copyright© 2019 Ferrata Storti Foundation.)
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- 2019
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15. "Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.
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Chapiro E, Lesty C, Gabillaud C, Durot E, Bouzy S, Armand M, Le Garff-Tavernier M, Bougacha N, Struski S, Bidet A, Laharanne E, Barin C, Veronese L, Prié N, Eclache V, Gaillard B, Michaux L, Lefebvre C, Gaillard JB, Terré C, Penther D, Bastard C, Nadal N, Fert-Ferrer S, Auger N, Godon C, Sutton L, Tournilhac O, Susin SA, and Nguyen-Khac F
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- Abnormal Karyotype, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Genes, p53, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Neoplasm Invasiveness genetics, Prognosis, Retrospective Studies, Chromosome Deletion, Chromosomes, Human, Pair 17 ultrastructure, Chromosomes, Human, Pair 8 ultrastructure, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Translocation, Genetic, Trisomy
- Abstract
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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16. Looking for Broken TAD Boundaries and Changes on DNA Interactions: Clinical Guide to 3D Chromatin Change Analysis in Complex Chromosomal Rearrangements and Chromothripsis.
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Yauy K, Gatinois V, Guignard T, Sati S, Puechberty J, Gaillard JB, Schneider A, and Pellestor F
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- Computational Biology methods, DNA Copy Number Variations, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics methods, Gene Rearrangement, Genetic Association Studies, Humans, Promoter Regions, Genetic, Web Browser, Chromothripsis, Genomics methods, Translocation, Genetic
- Abstract
Apparition of next-generation sequencing (NGS) was a breakthrough on knowledge of genome structure. Bioinformatic tools are a key point to analyze this huge amount of data from NGS and characterize the three-dimensional organization of chromosomes. This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. Their pathogenic impact on clinical phenotype and gene misexpression can also be evaluated with annotated databases.
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- 2018
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17. Single-molecule DNA sequencing of acute myeloid leukemia and myelodysplastic syndromes with multiple TP53 alterations.
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Lodé L, Ameur A, Coste T, Ménard A, Richebourg S, Gaillard JB, Le Bris Y, Béné MC, Lavabre-Bertrand T, and Soussi T
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- Alleles, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Mutation, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy, Prognosis, Sequence Analysis, DNA, Genetic Variation, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics, Tumor Suppressor Protein p53 genetics
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- 2018
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18. An incidental finding of maternal multiple myeloma by non invasive prenatal testing.
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Imbert-Bouteille M, Chiesa J, Gaillard JB, Dorvaux V, Altounian L, Gatinois V, Mousty E, Finge S, Bourquard P, Vermeesch JR, Legius E, and Vandenberghe P
- Subjects
- Adult, Female, Humans, Multiple Myeloma genetics, Pregnancy, Pregnancy Complications, Neoplastic genetics, Sequence Analysis, DNA, Genetic Testing, Incidental Findings, Maternal Serum Screening Tests, Multiple Myeloma diagnosis, Pregnancy Complications, Neoplastic diagnosis
- Published
- 2017
- Full Text
- View/download PDF
19. New chimeric RNAs in acute myeloid leukemia.
- Author
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Rufflé F, Audoux J, Boureux A, Beaumeunier S, Gaillard JB, Bou Samra E, Megarbane A, Cassinat B, Chomienne C, Alves R, Riquier S, Gilbert N, Lemaitre JM, Bacq-Daian D, Bougé AL, Philippe N, and Commes T
- Abstract
Background: High-throughput next generation sequencing (NGS) technologies enable the detection of biomarkers used for tumor classification, disease monitoring and cancer therapy. Whole-transcriptome analysis using RNA-seq is important, not only as a means of understanding the mechanisms responsible for complex diseases but also to efficiently identify novel genes/exons, splice isoforms, RNA editing, allele-specific mutations, differential gene expression and fusion-transcripts or chimeric RNA (chRNA). Methods: We used Crac, a tool that uses genomic locations and local coverage to classify biological events and directly infer splice and chimeric junctions within a single read. Crac's algorithm extracts transcriptional chimeric events irrespective of annotation with a high sensitivity, and CracTools was used to aggregate, annotate and filter the chRNA reads. The selected chRNA candidates were validated by real time PCR and sequencing. In order to check the tumor specific expression of chRNA, we analyzed a publicly available dataset using a new tag search approach. Results: We present data related to acute myeloid leukemia (AML) RNA-seq analysis. We highlight novel biological cases of chRNA, in addition to previously well characterized leukemia chRNA. We have identified and validated 17 chRNAs among 3 AML patients: 10 from an AML patient with a translocation between chromosomes 15 and 17 (AML-t(15;17), 4 from patient with normal karyotype (AML-NK) 3 from a patient with chromosomal 16 inversion (AML-inv16). The new fusion transcripts can be classified into four groups according to the exon organization. Conclusions: All groups suggest complex but distinct synthesis mechanisms involving either collinear exons of different genes, non-collinear exons, or exons of different chromosomes. Finally, we check tumor-specific expression in a larger RNA-seq AML cohort and identify new AML biomarkers that could improve diagnosis and prognosis of AML., Competing Interests: Competing interests: No competing interests were disclosed.
- Published
- 2017
- Full Text
- View/download PDF
20. Association of myeloproliferative and lymphoproliferative disorders.
- Author
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Gaillard JB, Carillo S, Henry L, Jourdan E, and Lavabre-Bertrand T
- Subjects
- Biopsy, Bone Marrow pathology, Female, Humans, Lymphoproliferative Disorders diagnosis, Male, Middle Aged, Myeloproliferative Disorders diagnosis, Pedigree, Lymphoproliferative Disorders complications, Myeloproliferative Disorders complications
- Published
- 2012
21. Monosomal karyotype routinely defines a poor prognosis subgroup in acute myeloid leukemia and is frequently associated with TP53 deletion.
- Author
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Gaillard JB, Chiesa J, Reboul D, Arnaud A, Brun S, Donadio D, Exbrayat C, Wickenhauser S, Bourquard P, Jourdan E, and Lavabre-Bertrand T
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Prognosis, Young Adult, Abnormal Karyotype, Gene Deletion, Leukemia, Myeloid, Acute genetics, Monosomy, Tumor Suppressor Protein p53 genetics
- Published
- 2012
- Full Text
- View/download PDF
22. Exon 7 deletion in the bcr-abl gene is frequent in chronic myeloid leukemia patients and is not correlated with resistance against imatinib.
- Author
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Gaillard JB, Arnould C, Bravo S, Donadio D, Exbrayat C, Jourdan E, Reboul D, Chiesa J, and Lavabre-Bertrand T
- Subjects
- Antineoplastic Agents therapeutic use, Benzamides, Cohort Studies, DNA Mutational Analysis, Exons, Gene Deletion, Gene Frequency, Genetic Association Studies, Genetic Testing methods, Humans, Imatinib Mesylate, Nucleic Acid Denaturation genetics, Protein Isoforms genetics, Temperature, Drug Resistance, Neoplasm genetics, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Piperazines therapeutic use, Pyrimidines therapeutic use
- Abstract
Chronic myeloid leukemia (CML) patients treated with imatinib develop frequent resistance generally due to a point mutation. Recently, large rearrangements of abl sequence have also been described. In this study, we focused on the complete deletion of exon 7. We screened for bcr-abl(delexon7) in 63 resistant patients by high-resolution melting (HRM) analysis and direct sequencing. Moreover, we analyzed expression of abl(delexon7) and bcr-abl(delexon7) in 17 CML patients at diagnosis, 32 patients at resistance, and 20 negative controls by quantitative PCR or fragment length analysis. bcr-abl(delexon7) was detected on 34 (54%) among 63 resistant patients by HRM, showing an increase in the sensitivity of screening, because only 3.2% could be detected by direct sequencing. This deletion was not associated with a point mutation (P = 0.3362). In addition, abl(delexon7) was found in all tested samples with the same pattern of expression, suggesting an alternative splicing mechanism. In the bcr-abl component, there was no statistical difference between CML patients at diagnosis and resistant patients (P = 0.2815) as regarding bcr-abl(delexon7) proportion, thus arguing against involvement of deletion in resistance. Moreover, among two patients harboring bcr-abl(delexon7) at diagnosis, one experienced a complete disappearance of this transcript, and the other decreased >75% at resistance. In conclusion, bcr-abl(delexon7) is frequently observed in CML patients when using sensitive techniques. It seems to be the result of an alternative splicing mechanism and to be independent from the occurrence of resistance., (©2010 AACR.)
- Published
- 2010
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23. A fenugreek seed extract selectively reduces spontaneous fat intake in overweight subjects.
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Chevassus H, Gaillard JB, Farret A, Costa F, Gabillaud I, Mas E, Dupuy AM, Michel F, Cantié C, Renard E, Galtier F, and Petit P
- Subjects
- Adolescent, Adult, Anti-Obesity Agents adverse effects, Antioxidants metabolism, Blood Glucose drug effects, Body Weight drug effects, Cholesterol metabolism, Energy Intake drug effects, Energy Metabolism drug effects, Herbal Medicine, Humans, Insulin blood, Male, Middle Aged, Overweight metabolism, Plant Extracts adverse effects, Anti-Obesity Agents therapeutic use, Overweight drug therapy, Phytotherapy, Plant Extracts therapeutic use, Seeds, Trigonella
- Abstract
Purpose: Fenugreek seeds (Trigonella foenum-graecum L.) have long been used as a herbal medicine for treating metabolic and nutritive dysfunctions. They have been shown to modulate feeding behaviour in animals. We have recently observed a selective decrease in fat consumption in healthy normal weight volunteers treated with a hydro-alcoholic seed extract. However, strong clinical data on the effects of fenugreek seeds on energy intake are lacking, especially in overweight individuals. The aim of our study was to investigate the effects of a repeated administration of a fenugreek seed extract on the eating behaviour of overweight subjects., Methods: Thirty-nine healthy overweight male volunteers completed a 6-week double-blind randomized placebo-controlled parallel trial of a fixed dose of a fenugreek seed extract. Main endpoints were energy intake (dietary records and meal test), weight, fasting and post-absorptive glucose and insulin, appetite/satiety scores and oxidative parameters., Results: Daily fat consumption, expressed as the ratio fat reported energy intake/total energy expenditure (fat-REI/TEE), was significantly decreased in our overweight subjects administered the fenugreek seed extract relative to those receiving the placebo (fat-REI/TEE 0.26 +/- 0.02 vs. 0.30 +/- 0.01, respectively; P = 0.032). We also observed a significant decrease in the insulin/glucose ratio in subjects treated with fenugreek seed extract relative to the placebo group (0.89 +/- 0.09 vs. 1.06 +/- 0.10 mUI mmol(-1), respectively; P = 0.044). No significant effect was observed on weight, appetite/satiety scores or oxidative parameters., Conclusion: The repeated administration of a fenugreek seed extract slightly but significantly decreased dietary fat consumption in healthy overweight subjects in this short-term study.
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- 2010
- Full Text
- View/download PDF
24. [Extended-spectrum beta-lactamases-producing Stenotrophomonas maltophilia strains: CTX-M enzymes detection and virulence study].
- Author
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Lavigne JP, Gaillard JB, Bourg G, Tichit C, Lecaillon E, and Sotto A
- Subjects
- Aged, Aged, 80 and over, Animals, Caenorhabditis elegans microbiology, Female, France epidemiology, Genes, Bacterial, Genotype, Gram-Negative Bacterial Infections epidemiology, Gram-Negative Bacterial Infections microbiology, Humans, Male, Middle Aged, Population Surveillance, R Factors genetics, Species Specificity, Stenotrophomonas maltophilia classification, Stenotrophomonas maltophilia genetics, Stenotrophomonas maltophilia pathogenicity, Substrate Specificity, Virulence genetics, beta-Lactamases classification, beta-Lactamases genetics, Drug Resistance, Multiple, Bacterial genetics, Stenotrophomonas maltophilia enzymology, beta-Lactam Resistance genetics, beta-Lactamases analysis
- Abstract
Objective: To study the beta-lactamases content of Stenotrophomonas maltophilia strains and to evaluate the virulence potential of these strains with the in vivo Caenorhabditis elegans model., Methodology: From 1st January 2006 to 31st December 2006, a monitoring programme to study multidrug resistant Gram-negative bacteria including extended-spectrum beta-lactamases (ESBL)-producing S. maltophilia was conducted at Nîmes University Hospital and Perpignan Hospital. The ESBL production was confirmed by the double-disk synergy test using ceftazidime, cefotaxime and cefepime disks associated with clavulanic acid disk. The strains were characterized phenotypically (beta-lactamase[s] identification) and genotypically (pulsed-field gel electrophoresis, plasmid analysis) and evaluated for their virulence with the in vivo nematode C. elegans model (establishment of survival curves [LT50])., Results: Twelve ESBL-producing S. maltophilia strains were isolated in eight patients (median age: 65 years+/-19) mainly during skin infections (41.7%). The ESBL content revealed the presence of four CTX-M-15-producing strains at the same patient. The analysis by ECP confirmed that the four strains were identical. The plasmid analysis demonstrated that the plasmid carrying CTX-M-15 in the worldwide clonal Escherichia coli O25-ST131 strain and S. maltophilia were different. The C. elegans model confirmed that S. maltophilia strains presented a low virulence potential (LT50=4.5days+/-0.5 according to the strains and nematode death in 10days+/-1) whatever their resistance., Conclusion: For the first time in France, a CTX-M-15-producing S. maltophilia strain has been identified. The in vivo model confirmed that these bacteria have a low potential virulence. However, these strains were isolated from "immunocompromised" and multihospital patients demonstrating the necessary monitoring of these patients. The CTX-M after diffusing in hospitals and community in E. coli strains seem to spread in other Gram-negative bacteria.
- Published
- 2008
- Full Text
- View/download PDF
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