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Determining the origin of synchronous multifocal bladder cancer by exome sequencing

Overview of attention for article published in BMC Cancer, November 2015
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  • Above-average Attention Score compared to outputs of the same age (57th percentile)
  • Good Attention Score compared to outputs of the same age and source (70th percentile)

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Title
Determining the origin of synchronous multifocal bladder cancer by exome sequencing
Published in
BMC Cancer, November 2015
DOI 10.1186/s12885-015-1859-8
Pubmed ID
Authors

Ömer Acar, Ezgi Özkurt, Gulfem Demir, Hilal Saraç, Can Alkan, Tarık Esen, Mehmet Somel, Nathan A. Lack

Abstract

Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours. To better understand the genetic lineage of these tumours we conducted exome sequencing of synchronous multifocal pTa urothelial bladder cancers at a high depth, using multiple samples from three patients. Phylogenetic analysis of high confidence single nucleotide variants (SNV) demonstrated that the sequenced multifocal bladder cancers arose from a clonal origin in all three patients (bootstrap value 100 %). Interestingly, in two patients the most common type of tumour-associated SNVs were cytosine mutations of TpC* dinucleotides (Fisher's exact test p < 10(-41)), likely caused by APOBEC-mediated deamination. Incorporating these results into our clonal model, we found that TpC* type mutations occurred 2-5× more often among SNVs on the ancestral branches than in the more recent private branches (p < 10(-4)) suggesting that TpC* mutations largely occurred early in the development of the tumour. These results demonstrate that synchronous multifocal bladder cancers frequently arise from a clonal origin. Our data also suggests that APOBEC-mediated mutations occur early in the development of the tumour and may be a driver of tumourigenesis in non-muscle invasive urothelial bladder cancer.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Turkey 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 22%
Researcher 7 17%
Student > Doctoral Student 6 15%
Student > Master 4 10%
Professor 3 7%
Other 10 24%
Unknown 2 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 11 27%
Medicine and Dentistry 10 24%
Biochemistry, Genetics and Molecular Biology 9 22%
Social Sciences 2 5%
Psychology 1 2%
Other 3 7%
Unknown 5 12%
Attention Score in Context

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 11 November 2015.
All research outputs
#7,448,418
of 22,771,140 outputs
Outputs from BMC Cancer
#2,060
of 8,280 outputs
Outputs of similar age
#96,422
of 284,724 outputs
Outputs of similar age from BMC Cancer
#70
of 260 outputs
Altmetric has tracked 22,771,140 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,280 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 68% 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 284,724 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 57% of its contemporaries.
We're also able to compare this research output to 260 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 70% of its contemporaries.