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2 results on '"MESH : Cytidine Deaminase"'

1. Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo

Author

Denise Guetard, Marc Sitbon, Jean-Pierre Vartanian, Anne Keriel, Myrtille Renard, Simon Wain-Hobson, Vincent Petit, Rétrovirologie Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Hypoxanthine Phosphoribosyltransferase, MESH : Molecular Sequence Data, MESH : RNA, Messenger, MESH : DNA, Complementary, MESH : NIH 3T3 Cells, viruses, Muscle Proteins, MESH: Base Sequence, Nucleic Acid Denaturation, MESH : Retroviridae Infections, MESH: Animals, Newborn, Mice, chemistry.chemical_compound, MESH : Hypoxanthine Phosphoribosyltransferase, Structural Biology, Murine leukemia virus, MESH : RNA, MESH: Animals, APOBEC Deaminases, MESH : Cytidine Deaminase, Gammaretrovirus, MESH : Muscle Proteins, 0303 health sciences, biology, Nucleotides, MESH : Animals, Newborn, 030302 biochemistry & molecular biology, MESH: Leukemia Virus, Murine, Cytidine, Cytidine deaminase, MESH: Apolipoproteins B, 3. Good health, Leukemia Virus, Murine, MESH: Retroviridae Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : Mutation, MESH: Genome, Viral, MESH : Genome, Viral, MESH : Leukemia Virus, Murine, MESH : Nucleic Acid Denaturation, APOBEC, DNA, Complementary, MESH: Mutation, APOBEC-1 Deaminase, Molecular Sequence Data, MESH: Leukemia, Experimental, Genome, Viral, MESH: Nucleic Acid Denaturation, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Muscle Proteins, 03 medical and health sciences, MESH: RNA, Cytidine Deaminase, MESH : Mice, MESH : RNA Editing, Animals, Humans, MESH: RNA Editing, RNA, Messenger, MESH: Mice, Molecular Biology, Apolipoproteins B, MESH: RNA, Messenger, MESH: Cytidine Deaminase, 030304 developmental biology, Messenger RNA, Leukemia, Experimental, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, APOBEC1, MESH : Humans, MESH: Tumor Virus Infections, RNA, MESH : Apolipoproteins B, MESH: DNA, Complementary, biology.organism_classification, MESH: Hypoxanthine Phosphoribosyltransferase, Molecular biology, MESH: Nucleotides, Tumor Virus Infections, Animals, Newborn, chemistry, Mutation, NIH 3T3 Cells, MESH : Nucleotides, MESH : Leukemia, Experimental, MESH : Base Sequence, MESH : Animals, RNA Editing, MESH : Tumor Virus Infections, Retroviridae Infections, MESH: NIH 3T3 Cells
Abstract

International audience; Mammalian APOBEC molecules comprise a large family of cytidine deaminases with specificity for RNA and single-stranded DNA (ssDNA). APOBEC1s are invariably highly specific and edit a single residue in a cellular mRNA, while the cellular targets for APOBEC3s are not clearly established, although they may curtail the transposition of some retrotransposons. Two of the seven member human APOBEC3 enzymes strongly restrict human immunodeficiency virus type 1 in vitro and in vivo. We show here that ssDNA hyperediting of an infectious exogenous gammaretrovirus, the Friend-murine leukemia virus, by murine APOBEC1 and APOBEC3 deaminases occurs in vitro. Murine APOBEC1 was able to hyperdeaminate cytidine residues in murine leukemia virus genomic RNA as well. Analysis of the edited sites shows that the deamination in vivo was due to mouse APOBEC1 rather than APOBEC3. Furthermore, murine APOBEC1 is able to hyperedit its primary substrate in vivo, the apolipoprotein B mRNA, and a variety of heterologous RNAs. In short, murine APOBEC1 is a hypermutator of both RNA and ssDNA in vivo, which could exert occasional side effects upon overexpression.

Published
2009

2. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab

Author

Pierre Feugier, Eric Labouyrie, Hervé Tilly, Felix Reyes, A. de Reyniès, David S. Rickman, Françoise Berger, Corinne Haioun, Gilles Salles, Karen Leroy, Christian Gisselbrecht, Thierry Jo Molina, Christian Bastard, Bertrand Coiffier, J-P Jais, Josette Brière, P. Gaulard, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), Programme CIT, Ligue Nationale Contre le Cancer, Service d'Anatomo-Pathologie, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'anatomo-pathologie [Paris], Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de pathologie [Mondor], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Anatomie et Cytologie Pathologiques, Service d'Hématologie, CRLCC Henri Becquerel, Service de génétique oncologique, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Guellaen, Georges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), Ligue Nationale Contre le Cancer (LNCC), Hospices Civils de Lyon (HCL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Oncology, Male, Cellular immunity, MESH: Cytoskeletal Proteins, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH: Metalloproteins, MESH : Aged, MESH: Antibodies, Monoclonal, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 80 and over, MESH : Cytidine Deaminase, Aged, 80 and over, 0303 health sciences, Hematology, MESH: Middle Aged, MESH : Reverse Transcriptase Polymerase Chain Reaction, Antibodies, Monoclonal, LIM Domain Proteins, Diffuse, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Vincristine, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Rituximab, MESH : DNA-Binding Proteins, MESH : Vincristine, medicine.medical_specialty, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Doxorubicin, MESH: Forkhead Transcription Factors, Large B-Cell, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Cyclophosphamide, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH: Cyclophosphamide, MESH : Prednisone, MESH : Cytoskeletal Proteins, medicine.disease, Lymphoma, Cytoskeletal Proteins, rab GTP-Binding Proteins, Immunology, Diffuse large B-cell lymphoma, MESH: Female, MESH: Prednisone, Cancer Research, MESH : rab GTP-Binding Proteins, APOBEC-3G Deaminase, CHOP, MESH : Lymphoma, Large B-Cell, Diffuse, Antibodies, Monoclonal, Murine-Derived, International Prognostic Index, MESH: Aged, 80 and over, MESH : Metalloproteins, immune system diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, Monoclonal, MESH : Female, MESH : Cyclophosphamide, MESH: Aged, Reverse Transcriptase Polymerase Chain Reaction, Forkhead Transcription Factors, Middle Aged, DNA-Binding Proteins, MESH : Forkhead Transcription Factors, MESH : Antibodies, Monoclonal, Female, Lymphoma, Large B-Cell, Diffuse, MESH : Repressor Proteins, medicine.drug, MESH : Male, MESH: Vincristine, Biology, Antibodies, MESH: Multivariate Analysis, Proto-Oncogene Proteins, Internal medicine, Cytidine Deaminase, Metalloproteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Doxorubicin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Cytidine Deaminase, Gene Expression Profiling, MESH : Multivariate Analysis, MESH: Male, Repressor Proteins, MESH: rab GTP-Binding Proteins, Doxorubicin, Multivariate Analysis, Prednisone, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: DNA-Binding Proteins
Abstract

International audience; Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.

Published
2008

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