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Clonal Architectures and Driver Mutations in Metastatic Melanomas

Overview of attention for article published in PLoS ONE, January 2014
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (63rd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

Mentioned by

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2 tweeters
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1 Facebook page

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25 Mendeley
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Title
Clonal Architectures and Driver Mutations in Metastatic Melanomas
Published in
PLoS ONE, January 2014
DOI 10.1371/journal.pone.0111153
Pubmed ID
Authors

Li Ding, Minjung Kim, Krishna L Kanchi, Nathan D Dees, Charles Lu, Malachi Griffith, David Fenstermacher, Hyeran Sung, Christopher A Miller, Brian Goetz, Michael C Wendl, Obi Griffith, Lynn A Cornelius, Gerald P Linette, Joshua F McMichael, Vernon K Sondak, Ryan C Fields, Timothy J Ley, James J Mulé, Richard K Wilson, Jeffrey S Weber

Abstract

To reveal the clonal architecture of melanoma and associated driver mutations, whole genome sequencing (WGS) and targeted extension sequencing were used to characterize 124 melanoma cases. Significantly mutated gene analysis using 13 WGS cases and 15 additional paired extension cases identified known melanoma genes such as BRAF, NRAS, and CDKN2A, as well as a novel gene EPHA3, previously implicated in other cancer types. Extension studies using tumors from another 96 patients discovered a large number of truncation mutations in tumor suppressors (TP53 and RB1), protein phosphatases (e.g., PTEN, PTPRB, PTPRD, and PTPRT), as well as chromatin remodeling genes (e.g., ASXL3, MLL2, and ARID2). Deep sequencing of mutations revealed subclones in the majority of metastatic tumors from 13 WGS cases. Validated mutations from 12 out of 13 WGS patients exhibited a predominant UV signature characterized by a high frequency of C->T transitions occurring at the 3' base of dipyrimidine sequences while one patient (MEL9) with a hypermutator phenotype lacked this signature. Strikingly, a subclonal mutation signature analysis revealed that the founding clone in MEL9 exhibited UV signature but the secondary clone did not, suggesting different mutational mechanisms for two clonal populations from the same tumor. Further analysis of four metastases from different geographic locations in 2 melanoma cases revealed phylogenetic relationships and highlighted the genetic alterations responsible for differential drug resistance among metastatic tumors. Our study suggests that clonal evaluation is crucial for understanding tumor etiology and drug resistance in melanoma.

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 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 4%
Unknown 24 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 40%
Student > Master 5 20%
Researcher 5 20%
Professor 1 4%
Student > Bachelor 1 4%
Other 3 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 11 44%
Medicine and Dentistry 8 32%
Biochemistry, Genetics and Molecular Biology 6 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 05 January 2015.
All research outputs
#2,303,584
of 6,334,604 outputs
Outputs from PLoS ONE
#39,430
of 98,011 outputs
Outputs of similar age
#54,978
of 154,090 outputs
Outputs of similar age from PLoS ONE
#1,325
of 2,957 outputs
Altmetric has tracked 6,334,604 research outputs across all sources so far. This one has received more attention than most of these and is in the 63rd percentile.
So far Altmetric has tracked 98,011 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.7. This one has gotten more attention than average, scoring higher than 59% 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 154,090 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 2,957 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 54% of its contemporaries.