scholarly journals Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours

2019 ◽  
Vol 85 (6) ◽  
pp. 1227-1238 ◽  
Author(s):  
R. Cohen ◽  
L. H. Preta ◽  
V. Joste ◽  
E. Curis ◽  
O. Huillard ◽  
...  
Keyword(s):  
Interindividual Variability ◽  
Cytidine Deaminase ◽  
Solid Tumours ◽  
Cytidine Deaminase Activity

Cytidine deaminase activity of human normal and malignant lymphoid cells

1985 ◽  
Vol 147 (2) ◽  
pp. 67-74 ◽  
Author(s):  
Jean-Louis Pérignon ◽  
Jacques Chaléon ◽  
Guy Leverger ◽  
Anne-Marie Houllier ◽  
Laure Thuillier ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Lymphoid Cells ◽  
Cytidine Deaminase Activity

Cytidine Deaminase Activity Assessment to Select Perioperative Chemotherapy Regimen in Localized Bladder Cancer

2017 ◽  
Vol 15 (3) ◽  
pp. e493-e495 ◽  
Author(s):  
Clemence Henon ◽  
Olivier Huillard ◽  
Laure-Hélène Preta ◽  
Benoit Blanchet ◽  
Francois Goldwasser ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Chemotherapy Regimen ◽  
Cytidine Deaminase ◽  
Perioperative Chemotherapy ◽  
Activity Assessment ◽  
Cytidine Deaminase Activity

Clonal MLL Fusions with a Signature of Activation Induced Cytidine Deaminase Activity,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3444-3444
Author(s):  
Bay T Ho ◽  
Shyh-Jen Shih ◽  
Sheetal P Singh ◽  
Manuel O Diaz ◽  
Dawei Lin ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
B Cell Lymphoma ◽  
Negative Regulator ◽  
Fusion Process ◽  
Common Finding ◽  
Common Mechanism ◽  
Cell Phenotype ◽  
Dna Breaks ◽  
Cytidine Deaminase Activity ◽  
Activation Induced Cytidine Deaminase

Abstract Abstract 3444 The MLL gene, encoding a histone methyl transferase, fuses with multiple different partner genes and is a common finding in patients with AML and ALL. This multiplicity of partners is in stark contrast to other fusion oncogenes such as BCR-ABL in CML or PML-RARA in APL, where fusions between the same genes predominate and which has aided the design of targeted therapy. In order to understand the fusion process in more detail, a hot spot for both MLL cleavage and gene fusion adjacent to exon 12 was examined in a series of breast cancer and lymphoma patients, using inverse PCR (IPCR). All patients received chemotherapy containing drugs targeting Topoisomerase II and samples of blood were examined both before and after therapy. Of the fifty patients enrolled in the study a subset was also examined by IPCR, parallel sequencing and custom bioinformatic analysis. The advantage of this approach is that all possible rearrangements may be examined within a single sample. In addition, the technique also records all sequences at the same location that are uninvolved in a translocation. The blood of three out of four patients examined in this way contained no evidence of MLL rearrangements. However in one patient, with a diagnosis of diffuse large B cell lymphoma, a total of thirteen MLL rearrangements were identified that were present prior to therapy. The majority of the fusions were detected for up to 6 months after the end of chemotherapy indicating they were likely of clonal origin. Of the thirteen fusions, five were predicted to provide functional fusion proteins and these included MLL-MLLT3 (AF9), the most common MLL fusion in myeloid leukemia. The remaining fusions predicted to generate functional proteins involved USP46, FER1L5, CCNJL and NKD1. None of these have been previously identified in clinical specimens of MLL linked disease. However, NKD1 is a negative regulator of the WNT pathway that has been linked to the maintenance of the stem cell phenotype in AML. In order to understand the fusion process in more detail, each fusion breakpoint was examined. All thirteen MLL fusions contained microhomology at the breakpoint, ranging from 1 to 6 bp, indicating NHEJ as the likely pathway generating the fusions. Though the presence of microhomology masked the precise breakpoint, using the 3' edge of microhomology as a reference, eight of the thirteen rearrangements were clustered within a 5 bp tract at the base of a putative stem-loop structure, as we have reported before. Such a restricted distribution of breakpoints found within a clonal population suggests a common mechanism is involved in either cleavage, and/or fusion, at this location. In order to address the mechanism driving these rearrangements, a screen of all sequenced material was undertaken. It was observed that within the residual sequenced material, a selective increase in C>T transitions were noted for two cytosines located within the 5bp breakpoint hotspot. The level of C>T transition was 50–100 fold higher than anywhere else within the sequence generated by IPCR. In addition, the region of C>T transition contained the WRC (A/T, A/G, C) motif characteristic of Activation-Induced Cytidine Deaminase (AID) attack. AID deaminates cytosine leading to a uracil which may be repaired by uracil-DNA glycosylase and the base excision repair (BER) pathway. AID has been implicated in both DNA breaks, via the BER pathway, and a linked increase in translocations. If the BER pathway fails to execute appropriately, a C>T transition may occur as the aberrantly located uracil undergoes replication at the next division. The presence of extensive C>T transitions therefore is indicative of both AID function and defective repair pathway(s). These factors may explain both the extensive number of rearrangements observed in this patient and the legacy C>T transitions from multiple AID attacks. Disclosures: No relevant conflicts of interest to declare.

scholarly journals FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135907 ◽  
Author(s):  
Cindy Serdjebi ◽  
Johan Gagnière ◽  
Jérôme Desramé ◽  
Francine Fein ◽  
Rosine Guimbaud ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Outcome ◽  
Cytidine Deaminase ◽  
Cytidine Deaminase Activity

scholarly journals The AKV Murine Leukemia Virus Is Restricted and Hypermutated by Mouse APOBEC3

2009 ◽  
Vol 83 (22) ◽  
pp. 11550-11559 ◽  
Author(s):  
Marc-André Langlois ◽  
Kristin Kemmerich ◽  
Cristina Rada ◽  
Michael S. Neuberger
Keyword(s):  
Cytidine Deaminase ◽  
Leukemia Virus ◽  
Endogenous Retrovirus ◽  
Mouse Strains ◽  
Restriction Factors ◽  
Retroviral Infection ◽  
Cytidine Deaminase Activity ◽  
Nucleotide Sequence Diversity ◽  
Apobec3 Proteins ◽  
Akr Mice

ABSTRACT APOBEC3 proteins are potent restriction factors against retroviral infection in primates. This restriction is accompanied by hypermutations in the retroviral genome that are attributable to the cytidine deaminase activity of the APOBEC3 proteins. Studies of nucleotide sequence diversity among endogenous gammaretroviruses suggest that the evolution of endogenous retroelements could have been shaped by the mutagenic cytidine deaminase activity of APOBEC3. In mice, however, APOBEC3 appears to restrict exogenous murine retroviruses in the absence of detectable levels of deamination. AKV is an endogenous retrovirus that is involved in causing a high incidence of thymic lymphoma in AKR mice. A comparative analysis of several mouse strains revealed a relatively low level of APOBEC3 expression in AKR mice. Here we show that endogenous mouse APOBEC3 restricts AKV infection and that this restriction likely reflects polymorphisms affecting APOBEC3 abundance rather than differences in the APOBEC3 isoforms expressed. We also observe that restriction of AKV by APOBEC3 is accompanied by G→A hypermutations in the viral genome. Our findings demonstrate that APOBEC3 acts as a restriction factor in rodents affecting the strain tropism of AKV, and they provide good support for the proposal that APOBEC3-mediated hypermutation contributed to the evolution of endogenous rodent retroviral genomes.

scholarly journals APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

2006 ◽  
Vol 203 (13) ◽  
pp. 2887-2893 ◽  
Author(s):  
Marjorie Pion ◽  
Angela Granelli-Piperno ◽  
Bastien Mangeat ◽  
Romaine Stalder ◽  
Rafael Correa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Messenger Rna ◽  
Cytidine Deaminase ◽  
Small Subset ◽  
Intrinsic Resistance ◽  
Susceptibility To Infection ◽  
Point Of Entry ◽  
Immature Dendritic Cells ◽  
Cytidine Deaminase Activity ◽  
Hiv 1

HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.

Determination of plasma cytidine deaminase activity by HPLC

1987 ◽  
Vol 2 (4) ◽  
pp. 148-151 ◽  
Author(s):  
D. A. Richards ◽  
R. A. Sherwood ◽  
D. Ndebele ◽  
B. F. Rocks
Keyword(s):  
Cytidine Deaminase ◽  
Cytidine Deaminase Activity

scholarly journals APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 366-375 ◽  
Author(s):  
Roni Nowarski ◽  
Ofer I. Wilner ◽  
Ori Cheshin ◽  
Or D. Shahar ◽  
Edan Kenig ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Genomic Dna ◽  
Cytidine Deaminase ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Lymphoma Cells ◽  
Direct Role ◽  
Cytidine Deaminase Activity ◽  
Retroviral Replication ◽  
Apobec3g Expression

Abstract APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

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