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Authors: Lei Lv, Tianwei Zhang, Qiyi Yi, Yun Huang, Zheng Wang, Heli Hou, Huan Zhang, Wei Zheng, Qiaomei Hao, Zongyou Guo, Howard J. Cooke and Qinghua Shi

Lei Lv

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China
These authors contributed equally to this work.

Tianwei Zhang

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China
These authors contributed equally to this work.

Qiyi Yi

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Yun Huang

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Zheng Wang

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Heli Hou

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Huan Zhang

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Wei Zheng

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Qiaomei Hao

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Zongyou Guo

Department of Dermatology; Brigham and Women’s Hospital and Harvard Skin Disease Research Center; Harvard Institutes of Medicine; Boston, MA USA

Howard J. Cooke

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China; MRC Human Genetics Unit and Institute of Genetics and Molecular Medicine; University of Edinburgh; Western General Hospital; Edinburgh, UK

Qinghua Shi

Corresponding author: qshi@ustc.edu.cn
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China; Hefei, China

Abstract:
Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells.

Received: May 16, 2012; Accepted: June 20, 2012

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