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Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets

Overview of attention for article published in European Urology, June 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (92nd percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

Mentioned by

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40 X users
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1 patent
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1 Facebook page
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1 research highlight platform

Citations

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268 Dimensions

Readers on

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229 Mendeley
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Title
Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets
Published in
European Urology, June 2017
DOI 10.1016/j.eururo.2017.05.032
Pubmed ID
Authors

Eugene J. Pietzak, Aditya Bagrodia, Eugene K. Cha, Esther N. Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F. Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E. Rosenberg, Dean F. Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B. Solit, Bernard H. Bochner

Abstract

Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. To identify genetic alterations with potential clinical implications in NMIBC. Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory. Comutation patterns and copy number alterations were compared across stage and grade. Associations between genomic alterations and recurrence after intravesical bacillus Calmette-Guérin (BCG) were estimated using Kaplan-Meier and Cox regression analyses. TERT promoter mutations (73%) and chromatin-modifying gene alterations (69%) were highly prevalent across grade and stage, suggesting these events occur early in tumorigenesis. ERBB2 or FGFR3 alterations were present in 57% of high-grade NMIBC tumors in a mutually exclusive pattern. DNA damage repair (DDR) gene alterations were seen in 30% (25/82) of high-grade NMIBC tumors, a rate similar to MIBC, and were associated with a higher mutational burden compared with tumors with intact DDR genes (p<0.001). ARID1A mutations were associated with an increased risk of recurrence after BCG (hazard ratio=3.14, 95% confidence interval: 1.51-6.51, p=0.002). Next-generation sequencing of treatment-naive index NMIBC tumors demonstrated that the majority of NMIBC tumors had at least one potentially actionable alteration that could serve as a target in rationally designed trials of intravesical or systemic therapy. DDR gene alterations were frequent in high-grade NMIBC and were associated with increased mutational load, which may have therapeutic implications for BCG immunotherapy and ongoing trials of systemic checkpoint inhibitors. ARID1A mutations were associated with an increased risk of recurrence after BCG therapy. Whether ARID1A mutations represent a predictive biomarker of BCG response or are prognostic in NMIBC patients warrants further investigation. Analysis of frequently mutated genes in superficial bladder cancer suggests potential targets for personalized treatment and predictors of treatment response, and also may help develop noninvasive tumor detection tests.

X Demographics

X Demographics

The data shown below were collected from the profiles of 40 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 229 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Korea, Republic of 1 <1%
Unknown 228 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 39 17%
Student > Ph. D. Student 33 14%
Student > Master 23 10%
Student > Bachelor 21 9%
Student > Doctoral Student 17 7%
Other 40 17%
Unknown 56 24%
Readers by discipline Count As %
Medicine and Dentistry 77 34%
Biochemistry, Genetics and Molecular Biology 53 23%
Agricultural and Biological Sciences 21 9%
Immunology and Microbiology 3 1%
Business, Management and Accounting 2 <1%
Other 6 3%
Unknown 67 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 31. 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 December 2020.
All research outputs
#1,260,349
of 25,382,440 outputs
Outputs from European Urology
#762
of 6,218 outputs
Outputs of similar age
#25,027
of 331,711 outputs
Outputs of similar age from European Urology
#24
of 92 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,218 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.1. This one has done well, scoring higher than 87% 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 331,711 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 92% of its contemporaries.
We're also able to compare this research output to 92 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.