Identification of Drivers of Aneuploidy in Breast Tumors

Katherine Pfister; Justyna L. Pipka; Colby Chiang; Yunxian Liu; Royden A. Clark; Ray Keller; Paul Skoglund; Michael J. Guertin; Ira M. Hall; P. Todd Stukenberg

doi:10.1016/j.celrep.2018.04.102

Cell Reports (May 2018)

Identification of Drivers of Aneuploidy in Breast Tumors

Katherine Pfister,
Justyna L. Pipka,
Colby Chiang,
Yunxian Liu,
Royden A. Clark,
Ray Keller,
Paul Skoglund,
Michael J. Guertin,
Ira M. Hall,
P. Todd Stukenberg

Affiliations

Katherine Pfister: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Justyna L. Pipka: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Colby Chiang: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Yunxian Liu: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Royden A. Clark: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Ray Keller: Department of Biology, University of Virginia, Charlottesville, VA 22908, USA
Paul Skoglund: Department of Biology, University of Virginia, Charlottesville, VA 22908, USA
Michael J. Guertin: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
Ira M. Hall: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
P. Todd Stukenberg: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA

DOI: https://doi.org/10.1016/j.celrep.2018.04.102
Journal volume & issue: Vol. 23, no. 9
pp. 2758 – 2769

Abstract

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Although aneuploidy is found in the majority of tumors, the degree of aneuploidy varies widely. It is unclear how cancer cells become aneuploid or how highly aneuploid tumors are different from those of more normal ploidy. We developed a simple computational method that measures the degree of aneuploidy or structural rearrangements of large chromosome regions of 522 human breast tumors from The Cancer Genome Atlas (TCGA). Highly aneuploid tumors overexpress activators of mitotic transcription and the genes encoding proteins that segregate chromosomes. Overexpression of three mitotic transcriptional regulators, E2F1, MYBL2, and FOXM1, is sufficient to increase the rate of lagging anaphase chromosomes in a non-transformed vertebrate tissue, demonstrating that this event can initiate aneuploidy. Highly aneuploid human breast tumors are also enriched in TP53 mutations. TP53 mutations co-associate with the overexpression of mitotic transcriptional activators, suggesting that these events work together to provide fitness to breast tumors.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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