Evidence map›Paper›PMID 26832928›Full record

ArticleBMC cancer2016

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

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

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026
    Article
  4. Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  17. A survey of chromosomal instability measures across mechanistic models.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Review
  19. Article
  20. Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Ryan A DenuDivision of Hematology/Oncology, Medical Scientist Training Program and the Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. rdenu@wisc.edu.
Lauren M ZasadilMolecular and Cellular Pharmacology Graduate Training Program and the Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, USA. lzasadil@wisc.edu.
Craig KanughWisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin, 53706, USA. craig.kanugh@slh.wisc.edu.
Jennifer LaffinWisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin, 53706, USA. jjlaffin@wisc.edu.
Beth A WeaverDepartment of Cell and Regenerative Biology and University of Wisconsin Carbone Cancer Center University of Wisconsin, Madison, WI, USA. baweaver@wisc.edu.
Mark E BurkardDepartment of Medicine, Division of Hematology/Oncology and University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 6059 WIMR, 1111 Highland Avenue, Madison, WI, 53705, USA. meburkard@medicine.wisc.edu.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
Training in Cancer Biology Training GrantT32CA009135 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1985 to 2024
$10.4M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Mitosis, Aneuploidy and CancerR01CA140458 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI WEAVER, BETH A · 2011 to 2015
$1.5M
Separation of late mitotic functions of polo-like kinase 1 with chemical geneticsR01GM097245 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 2011 to 2015
$1.4M
Identifying causes and consequences of centrosome amplification in cancerF30CA203271 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI DENU, RYAN AUSTIN · 2016 to 2019
$124k
NCI NIH HHS F30 CA203271NCI NIH HHS P30 CA014520NCI NIH HHS P30 CA086862NCI NIH HHS R01 CA140458NCI NIH HHS T32 CA009135NCI NIH HHS T32CA9135-37NIGMS NIH HHS R01 GM097245NIGMS NIH HHS T32 GM008688NIGMS NIH HHS T32 GM008692NIGMS NIH HHS T32GM008692
6 · The paper itself

Abstract

backgroundCentrosome 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.

methodsWe 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).

resultsCA 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.

conclusionsCA 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.

Indexed as

CentrosomeGene AmplificationPrognosisAdultAgedAged, 80 and overAntigensBreast NeoplasmsCell DedifferentiationCell Line, TumorChinaFemaleHumansIn Situ HybridizationMiddle AgedMitosisAntigenspericentrinPLK4 protein, humanProtein Serine-Threonine KinasesTubulin

Identifiers

PMID26832928
PMCPMC4734858
OpenAlexW2253467674

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.