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Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer

Overview of attention for article published in BMC Cancer, January 2016
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Citations

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Title
Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer
Published in
BMC Cancer, January 2016
DOI 10.1186/s12885-016-2083-x
Pubmed ID
Authors

Ryan A. Denu, Lauren M. Zasadil, Craig Kanugh, Jennifer Laffin, Beth A. Weaver, Mark E. Burkard

Abstract

Centrosome amplification (CA) has been reported in nearly all types of human cancer and is associated with deleterious clinical factors such as higher grade and stage. However, previous reports have not shown how CA affects cellular differentiation and clinical outcomes in breast cancer. We analyzed centrosomes by immunofluorescence and compared to ploidy and chromosomal instability (CIN) as assessed by 6-chromosome FISH in a cohort of 362 breast cancers with median clinical follow-up of 8.4 years. Centrosomes were recognized by immunofluorescence using antibodies for pericentriolar material (PCM; pericentrin) and centrioles (polyglutamylated tubulin). CA was experimentally induced in cell culture by overexpression of polo-like kinase 4 (PLK4). CA is associated with reduced all-cause and breast cancer-specific overall survival and recurrence-free survival. CA correlates strongly with high-risk subtypes (e.g. triple negative) and higher stage and grade, and the prognostic nature of CA can be explained largely by these factors. A strong correlation between CA and high tumor ploidy demonstrates that chromosome and centrosome doubling often occur in concert. CA is proposed to be a method of inducing CIN via aberrant mitotic cell divisions; consonant with this, we observed a strong correlation between CA and CIN in breast cancers. However, some CA tumors had low levels of CIN, indicating that protective mechanisms are at play, such as centrosome clustering during mitosis. Intriguingly, some high-risk tumors have more acentriolar centrosomes, suggesting PCM fragmentation as another mechanism of CA. In vitro induction of CA in two non-transformed human cell lines (MCF10A and RPE) demonstrated that CA induces a de-differentiated cellular state and features of high-grade malignancy, supporting the idea that CA intrinsically causes high-grade tumors. CA is associated with deleterious clinical factors and outcomes in breast cancer. Cell doubling events are the most prevalent causes of CA in cancer, although PCM fragmentation may be a secondary cause. CA promotes high-risk breast cancer in part by inducing high-grade features. These findings highlight the importance of centrosome aberrations in the biology of human breast cancer.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 1%
Unknown 77 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 26%
Student > Master 12 15%
Student > Bachelor 9 12%
Researcher 9 12%
Student > Doctoral Student 4 5%
Other 9 12%
Unknown 15 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 30 38%
Agricultural and Biological Sciences 19 24%
Medicine and Dentistry 6 8%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Arts and Humanities 1 1%
Other 4 5%
Unknown 15 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 03 February 2016.
All research outputs
#5,314,920
of 7,089,314 outputs
Outputs from BMC Cancer
#2,050
of 3,196 outputs
Outputs of similar age
#221,114
of 320,347 outputs
Outputs of similar age from BMC Cancer
#106
of 195 outputs
Altmetric has tracked 7,089,314 research outputs across all sources so far. This one is in the 13th percentile – i.e., 13% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,196 research outputs from this source. They receive a mean Attention Score of 3.3. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
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We're also able to compare this research output to 195 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.