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Oxidative stress-induced chromosome breaks within the ABL gene: a model for chromosome rearrangement in nasopharyngeal carcinoma

Overview of attention for article published in Human Genomics, June 2018
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Title
Oxidative stress-induced chromosome breaks within the ABL gene: a model for chromosome rearrangement in nasopharyngeal carcinoma
Published in
Human Genomics, June 2018
DOI 10.1186/s40246-018-0160-8
Pubmed ID
Authors

Sang-Nee Tan, Sai-Peng Sim, Alan Soo-Beng Khoo

Abstract

The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. During apoptosis, chromatin cleavage and DNA fragmentation occur. However, cells may undergo DNA repair and survive apoptosis. Non-homologous end joining (NHEJ) pathway has been known as the primary DNA repair system in human cells. The NHEJ process may repair DNA ends without any homology, although region of microhomology (a few nucleotides) is usually utilised by this DNA repair system. Cells that evade apoptosis via erroneous DNA repair may carry chromosomal aberration. Apoptotic nuclease was found to be associated with nuclear matrix during apoptosis. Matrix association region/scaffold attachment region (MAR/SAR) is the binding site of the chromosomal DNA loop structure to the nuclear matrix. When apoptotic nuclease is associated with nuclear matrix during apoptosis, it potentially cleaves at MAR/SAR. Cells that survive apoptosis via compromised DNA repair may carry chromosome rearrangement contributing to NPC tumourigenesis. The Abelson murine leukaemia (ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress-induced apoptosis. In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ. Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed.

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The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 24%
Student > Bachelor 4 16%
Student > Master 3 12%
Other 2 8%
Lecturer 1 4%
Other 1 4%
Unknown 8 32%
Readers by discipline Count As %
Medicine and Dentistry 5 20%
Biochemistry, Genetics and Molecular Biology 3 12%
Nursing and Health Professions 2 8%
Agricultural and Biological Sciences 1 4%
Environmental Science 1 4%
Other 4 16%
Unknown 9 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 June 2018.
All research outputs
#17,292,294
of 25,385,509 outputs
Outputs from Human Genomics
#389
of 564 outputs
Outputs of similar age
#220,555
of 341,728 outputs
Outputs of similar age from Human Genomics
#9
of 11 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 564 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,728 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.