A virus causes cancer by inducing massive chromosomal instability through cell fusion

Duelli, D. M., Padilla-Nash, H. M., Berman, D., Murphy, K. M., Ried, T., Lazebnik, Y. (March 2007) A virus causes cancer by inducing massive chromosomal instability through cell fusion. Current Biology, 17 (5). pp. 431-7. ISSN 0960-9822 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17320392
DOI: 10.1016/j.cub.2007.01.049

Abstract

Chromosomal instability (CIN) underlies malignant properties of many solid cancers and their ability to escape therapy, and it might itself cause cancer [1, 2]. CIN is sustained by deficiencies in proteins, such as the tumor suppressor p53 [3-5], that police genome integrity, but the primary cause of CIN in sporadic cancers remains uncertain [6, 7]. The primary suspects are mutations that deregulate telomere maintenance, or mitosis, yet such mutations have not been identified in the majority of sporadic cancers [6]. Alternatively, CIN could be caused by a transient event that destabilizes the genome without permanently affecting mechanisms of mitosis or proliferation [5, 8]. Here, we show that an otherwise harmless virus rapidly causes massive chromosomal instability by fusing cells whose cell cycle is deregulated by oncogenes. This synergy between fusion and oncogenes "randomizes" normal diploid human fibroblasts so extensively that each analyzed cell has a unique karyotype, and some produce aggressive, highly aneuploid, heterogeneous, and transplantable epithelial cancers in mice. Because many viruses are fusogenic, this study suggests that viruses, including those that have not been linked to carcinogenesis, can cause chromosomal instability and, consequently, cancer by fusing cells.

Item Type: Paper
Subjects: diseases & disorders > cancer
Investigative techniques and equipment > cell fusion
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome

organs, tissues, organelles, cell types and functions > organelles, types and functions > mitosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > telomeres
CSHL Authors:
Communities: CSHL labs > Labeznik lab
Depositing User: CSHL Librarian
Date: 6 March 2007
Date Deposited: 30 Nov 2011 21:09
Last Modified: 22 Mar 2018 19:34
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23004

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