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iScience. 2019 Sep 27;19:850-859. doi: 10.1016/j.isci.2019.08.043. Epub 2019 Aug 27.

Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations.

Author information

1
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Center for Cancer Target Discovery and Development (CTD(2)), UCSD Moores Cancer Center, La Jolla, CA 92093, USA; Division of Medical Genetics, UCSD School of Medicine, La Jolla, CA 92093, USA.
3
The Scripps Translational Science Institute, La Jolla, CA 9203, USA.
4
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: sreed@scripps.edu.

Abstract

Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This in turn promotes chromosomal damage during anaphase. Here we show that non-transformed human mammary epithelial cell clones that survive such aberrant mitoses have a specific and reproducible pattern of chromosomal Copy Number Alterations (CNAs) that we have characterized and termed the cyclin E CNA signature. Using a number of computational approaches, we show that this signature resembles one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. Analysis of the CNA profile of these clones provides a potential mechanism for cyclin E-mediated oncogenesis.

KEYWORDS:

Biological Sciences; Cancer; Cell Biology; Molecular Biology; Transcriptomics

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