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A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns

Overview of attention for article published in Nature, October 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (94th percentile)

Mentioned by

news
70 news outlets
blogs
3 blogs
twitter
244 X users
patent
6 patents
facebook
6 Facebook pages
wikipedia
1 Wikipedia page
googleplus
1 Google+ user

Citations

dimensions_citation
435 Dimensions

Readers on

mendeley
704 Mendeley
citeulike
8 CiteULike
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Title
A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns
Published in
Nature, October 2016
DOI 10.1038/nature19823
Pubmed ID
Authors

Faiyaz Notta, Michelle Chan-Seng-Yue, Mathieu Lemire, Yilong Li, Gavin W. Wilson, Ashton A. Connor, Robert E. Denroche, Sheng-Ben Liang, Andrew M. K. Brown, Jaeseung C. Kim, Tao Wang, Jared T. Simpson, Timothy Beck, Ayelet Borgida, Nicholas Buchner, Dianne Chadwick, Sara Hafezi-Bakhtiari, John E. Dick, Lawrence Heisler, Michael A. Hollingsworth, Emin Ibrahimov, Gun Ho Jang, Jeremy Johns, Lars G. T. Jorgensen, Calvin Law, Olga Ludkovski, Ilinca Lungu, Karen Ng, Danielle Pasternack, Gloria M. Petersen, Liran I. Shlush, Lee Timms, Ming-Sound Tsao, Julie M. Wilson, Christina K. Yung, George Zogopoulos, John M. S. Bartlett, Ludmil B. Alexandrov, Francisco X. Real, Sean P. Cleary, Michael H. Roehrl, John D. McPherson, Lincoln D. Stein, Thomas J. Hudson, Peter J. Campbell, Steven Gallinger

Abstract

Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.

X Demographics

X Demographics

The data shown below were collected from the profiles of 244 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 704 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 9 1%
United States 8 1%
France 2 <1%
Germany 2 <1%
Canada 2 <1%
Finland 1 <1%
Italy 1 <1%
Japan 1 <1%
Australia 1 <1%
Other 0 0%
Unknown 677 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 161 23%
Researcher 146 21%
Student > Bachelor 70 10%
Student > Master 57 8%
Student > Doctoral Student 46 7%
Other 115 16%
Unknown 109 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 235 33%
Medicine and Dentistry 133 19%
Agricultural and Biological Sciences 122 17%
Computer Science 15 2%
Immunology and Microbiology 11 2%
Other 56 8%
Unknown 132 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 704. 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 13 December 2022.
All research outputs
#29,488
of 25,559,053 outputs
Outputs from Nature
#2,739
of 98,240 outputs
Outputs of similar age
#537
of 326,615 outputs
Outputs of similar age from Nature
#57
of 1,022 outputs
Altmetric has tracked 25,559,053 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 98,240 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.6. This one has done particularly well, scoring higher than 97% 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 326,615 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 99% of its contemporaries.
We're also able to compare this research output to 1,022 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 94% of its contemporaries.