Cold Springs Harbor researchers propose viruses which fuse cells produce cancer cells

[Lani]

with chromosomal instability

CSHL Research Ties Harmless Viruses to Cancer [Cold Spring Harbor Laboratory]
Research led by Cold Spring Harbor Laboratory (CSHL) may link viruses that have been considered harmless to chromosomal instability (CIN) and cancer. "If the model that we propose is correct, protecting the body against viruses, or preventing the cell fusion that they cause may decrease the frequency of cancers and prevent their progression," said CSHL's lead investigator Yuri Lazebnik.

According to this model, cells can be made cancerous by viruses that fuse cells. Fusion abruptly unites two or three cells under the same membrane, a change that triggers massive CIN and creates diverse cells whose properties change over time. The researchers found that some of these cells can become cancerous.

The model that the researchers propose suggests that the best hope for controlling cancer is its prevention. If viruses can cause CIN, identifying and inactivating these viruses would help to decrease the incidence of the disease. This prognosis is consistent with the successes of preventative immunization against hepatitis B and papilloma viruses, which both cause cancer. Lazebnik and his CSHL colleague Dominik Duelli estimate that at least 18 of 29 virus families that infect human cells have species that fuse cells, which implies that CIN and cancer might be caused by viruses, even those that are considered harmless.

CSHL collaborated on this study with the Genetics Branch of the National Cancer Institute and the Johns Hopkins University Medical School. The paper's full citation is as follows: Dominik M. Duelli, Hesed M. Padilla-Nash David Berman, Kathleen M. Murphy, Thomas Ried, and Yuri Lazebnik.


and here is the abstract:
A Virus Causes Cancer by Inducing Massive Chromosomal Instability through Cell Fusion [Current Biology]
Chromosomal instability (CIN) underlies malignant properties of many solid cancers and their ability to escape therapy, and it might itself cause cancer. CIN is sustained by deficiencies in proteins, such as the tumor suppressor p53, that police genome integrity, but the primary cause of CIN in sporadic cancers remains uncertain. The primary suspects are mutations that deregulate telomere maintenance, or mitosis, yet such mutations have not been identified in the majority of sporadic cancers. Alternatively, CIN could be caused by a transient event that destabilizes the genome without permanently affecting mechanisms of mitosis or proliferation. 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.