Evidence map›Paper›PMID 26740101›Full record

ArticleJournal of hematology & oncology2016

Combined deletion of Xrcc4 and Trp53 in mouse germinal center B cells leads to novel B cell lymphomas with clonal heterogeneity.

Zhangguo Chen, Mihret T Elos, Sawanee S Viboolsittiseri, Katherine Gowan, Sonia M Leach, Michael Rice, Maxwell D Eder, Kenneth Jones, Jing H Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Zhangguo ChenDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Mihret T ElosDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Sawanee S ViboolsittiseriDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Katherine GowanDepartment of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Sonia M LeachDepartment of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.
Michael RiceDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Maxwell D EderDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Kenneth JonesDepartment of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Jing H WangDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA. jing.wang@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USNational Jewish Health · USUniversity of Colorado Denver · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Mechanisms promoting translocations and mature B cell lymphomasR01CA166325 · NCI · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG · 2012 to 2016
$1.7M
Genomic instability mediated via differential DNA repair mechanisms in B cellsR21CA184707 · NCI · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG · 2015 to 2016
$372k
NCATS NIH HHS UL1 TR001082NCI NIH HHS 3R01CA166325-02S1NCI NIH HHS R01 CA166325NCI NIH HHS R01CA166325NCI NIH HHS R21 CA184707NCI NIH HHS R21CA184707
6 · The paper itself

Abstract

backgroundActivated B lymphocytes harbor programmed DNA double-strand breaks (DSBs) initiated by activation-induced deaminase (AID) and repaired by non-homologous end-joining (NHEJ). While it has been proposed that these DSBs during secondary antibody gene diversification are the primary source of chromosomal translocations in germinal center (GC)-derived B cell lymphomas, this point has not been directly addressed due to the lack of proper mouse models.

methodsIn the current study, we establish a unique mouse model by specifically deleting a NHEJ gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in GC B cells, which results in the spontaneous development of B cell lymphomas that possess features of GC B cells.

resultsWe show that these NHEJ deficient lymphomas harbor translocations frequently targeting immunoglobulin (Ig) loci. Furthermore, we found that Ig translocations were associated with distinct mechanisms, probably caused by AID- or RAG-induced DSBs. Intriguingly, the AID-associated Ig loci translocations target either c-myc or Pvt-1 locus whereas the partners of RAG-associated Ig translocations scattered randomly in the genome. Lastly, these NHEJ deficient lymphomas harbor complicated genomes including segmental translocations and exhibit a high level of ongoing DNA damage and clonal heterogeneity.

conclusionsWe propose that combined NHEJ and p53 defects may serve as an underlying mechanism for a high level of genomic complexity and clonal heterogeneity in cancers.

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)Amino Acid SequenceAnimalsBase SequenceB-LymphocytesCells, CulturedClone CellsCytidine DeaminaseDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA End-Joining RepairGerminal CenterImmunoglobulin Heavy ChainsIn Situ Hybridization, FluorescenceKaplan-Meier EstimateLymphoma, B-CellAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseDNA-Binding ProteinsImmunoglobulin Heavy ChainsTumor Suppressor Protein p53XRCC4 protein, mouse

Identifiers

PMID26740101
PMCPMC4704435
OpenAlexW2224495827

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.