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Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers

Overview of attention for article published in Breast Cancer Research, June 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

Mentioned by

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2 tweeters
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4 patents
facebook
1 Facebook page

Citations

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177 Dimensions

Readers on

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211 Mendeley
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Title
Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers
Published in
Breast Cancer Research, June 2014
DOI 10.1186/bcr3670
Pubmed ID
Authors

Johnathan A Watkins, Sheeba Irshad, Anita Grigoriadis, Andrew NJ Tutt

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies have been found to be particularly effective in tumors that harbor deleterious germline or somatic mutations in the BRCA1 or BRCA2 genes, the products of which contribute to the conservative homologous recombination repair of DNA double-strand breaks. Nonetheless, several setbacks in clinical trial settings have highlighted some of the issues surrounding the investigation of PARP inhibitors, especially the identification of patients who stand to benefit from such drugs. One potential approach to finding this patient subpopulation is to examine the tumor DNA for evidence of a homologous recombination defect. However, although the genomes of many breast and ovarian cancers are replete with aberrations, the presence of numerous factors able to shape the genomic landscape means that only some of the observed DNA abnormalities are the outcome of a cancer cell's inability to faithfully repair DNA double-strand breaks. Consequently, recently developed methods for comprehensively capturing the diverse ways in which homologous recombination deficiencies may arise beyond BRCA1/2 mutation have used DNA microarray and sequencing data to account for potentially confounding features in the genome. Scores capturing telomeric allelic imbalance, loss of heterozygosity (LOH) and large scale transition score, as well as the total number of coding mutations are measures that summarize the total burden of certain forms of genomic abnormality. By contrast, other studies have comprehensively catalogued different types of mutational pattern and their relative contributions to a given tumor sample. Although at least one study to explore the use of the LOH scar in a prospective clinical trial of a PARP inhibitor in ovarian cancer is under way, limitations that result in a relatively low positive predictive value for these biomarkers remain. Tumors whose genome has undergone one or more events that restore high-fidelity homologous recombination are likely to be misclassified as double-strand break repair-deficient and thereby sensitive to PARP inhibitors and DNA damaging chemotherapies as a result of prior repair deficiency and its genomic scarring. Therefore, we propose that integration of a genomic scar-based biomarker with a marker of resistance in a high genomic scarring burden context may improve the performance of any companion diagnostic for PARP inhibitors.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 211 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 <1%
United Kingdom 2 <1%
Netherlands 1 <1%
Singapore 1 <1%
Germany 1 <1%
Unknown 204 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 55 26%
Student > Ph. D. Student 44 21%
Student > Master 23 11%
Other 11 5%
Student > Bachelor 11 5%
Other 33 16%
Unknown 34 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 57 27%
Medicine and Dentistry 55 26%
Agricultural and Biological Sciences 42 20%
Pharmacology, Toxicology and Pharmaceutical Science 3 1%
Engineering 3 1%
Other 8 4%
Unknown 43 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 07 April 2020.
All research outputs
#3,040,412
of 17,883,304 outputs
Outputs from Breast Cancer Research
#411
of 1,730 outputs
Outputs of similar age
#33,617
of 198,504 outputs
Outputs of similar age from Breast Cancer Research
#4
of 26 outputs
Altmetric has tracked 17,883,304 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,730 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one has done well, scoring higher than 76% 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 198,504 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.