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Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma

Overview of attention for article published in Molecular Cancer Research, March 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#21 of 1,982)
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

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10 news outlets
blogs
1 blog
twitter
4 X users
wikipedia
9 Wikipedia pages

Citations

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61 Dimensions

Readers on

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68 Mendeley
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Title
Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma
Published in
Molecular Cancer Research, March 2015
DOI 10.1158/1541-7786.mcr-14-0337
Pubmed ID
Authors

Erika A. Newman, Fujia Lu, Daniela Bashllari, Li Wang, Anthony W. Opipari, Valerie P. Castle

Abstract

In neuroblastoma (NB), MYCN genomic amplification and segmental chromosomal alterations including 1p or 11q loss of heterozygocity and/or 17q gain are associated with progression and poor clinical outcome. Segmental alterations are the strongest predictor of relapse and result from unbalanced translocations attributable to erroneous repair of chromosomal breaks. Although sequence analysis of affected genomic regions suggests these errors arise by non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSB), abnormalities in NHEJ have not been implicated in NB pathogenesis. On this basis, the hypothesis that an error-prone mechanism of NHEJ is critical for NB cell survival was tested. Plasmid-based DSB repair assays demonstrated efficient NHEJ activity in human NB cells with repair products that were error-prone relative to non-transformed cells. NB cells derived from tumorigenic neuroblastic phenotypes had differential DNA repair protein expression patterns compared to non-tumorigenic cells. Tumorigenic NB cells were deficient in DNA ligase IV (Lig4) and Artemis (DCLRE1C), mediators of canonical NHEJ. Conversely, enzymes required for an error-prone alternative NHEJ pathway (alt-NHEJ), DNA Ligase IIIα (Lig3), DNA Ligase I (Lig1), and poly (ADP-ribose) polymerase-1 protein (PARP1) were upregulated. Inhibition of Lig3 and Lig1 led to DSB accumulation and cell death, linking alt-NHEJ to cell survival in NB. NB cells demonstrated sensitivity to PARP1 inhibition (PARPi) that paralleled PARP1 expression. In a dataset of human NB patient tumors, overexpression of genes encoding alt-NHEJ proteins associated with poor survival. Implications: These findings provide insight into DNA repair fidelity in NB and identify components of the alt-NHEJ pathway as promising therapeutic targets.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 68 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 26%
Student > Bachelor 11 16%
Student > Master 6 9%
Student > Postgraduate 4 6%
Researcher 4 6%
Other 7 10%
Unknown 18 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 37%
Medicine and Dentistry 13 19%
Agricultural and Biological Sciences 9 13%
Psychology 1 1%
Pharmacology, Toxicology and Pharmaceutical Science 1 1%
Other 0 0%
Unknown 19 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 77. 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 06 October 2022.
All research outputs
#526,145
of 24,576,899 outputs
Outputs from Molecular Cancer Research
#21
of 1,982 outputs
Outputs of similar age
#7,025
of 291,166 outputs
Outputs of similar age from Molecular Cancer Research
#2
of 48 outputs
Altmetric has tracked 24,576,899 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,982 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 98% of its peers.
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 291,166 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 48 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.