Findings Implicate Virus as Skin Cancer Cause

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University of Pittsburgh

University of Pittsburgh scientists, led by Patrick Moore, MD, professor of microbiology and molecular genetics at Pitt School of Medicine and director of the Molecular Virology Program at the University of Pittsburgh Cancer Institute, Pennsylvania, recently discovered a virus that they have determined is the cause of Merkel cell carcinoma. Merkel cell carcinoma is an aggressive and potentially fatal form of skin cancer. The findings were published in an early online edition of the Proceedings of the National Academy of Sciences, and they put to rest the theory that the Merkel cell polyomavirus (MCV) only infects already-formed tumors. If that were the case, the researchers asserted, the virus would be a passenger rather than the driver of the disease.

In a paper published in Science earlier this year, Dr. Moore and his wife, Yuan Chang, MD, who co-directs their laboratory, reported their discovery of the virus and noted that it was found in 80% of Merkel cell tumors. They said that although as much as 16% of the population carries MCV, few people go on to develop the cancer.

Experiments in human tumors showed that the cancer develops in 2 steps. First, during active infection, MCV integrates into the host’s cell DNA, where it produces viral proteins that promote cancer formation. The tumors occur when a mutation removes part of a viral protein that the virus needs to replicate and infect other healthy cells. The virus then spreads only in conjunction with multiplication of the cancer cells.

“MCV infects normal cells before they turn into cancer cells,” Dr. Moore explained. “The virus could not have infected a tumor afterwards because it can no longer replicate. It looks very much like MCV is the culprit that causes the disease.”

The researchers propose 2 reasons why these mutations develop: if viral replication continues, the immune system recognizes the intruder and eliminates diseased cells; or, the viral replication itself leads to the death of the cancer cells. Both possibilities open promising avenues for finding better ways to kill Merkel cell cancer without harming healthy tissues.

Dr. Moore pointed out that “this research shows evolution within tumors on a molecular level,” nothing, “You can see the specific molecular steps.” The team’s current work could account for known Merkel cell carcinoma risk factors, such as ultraviolet exposure and ionizing radiation, both of which damage DNA and could trigger the viral mutations.

Although Merkel cell cancers are rare, half of patients who have an advanced form of the disease die within 9 months of diagnosis and two-thirds die within 2 years. The elderly and individuals with compromised immune systems are at greater risk of developing the cancer, which arises in skin nerve cells that respond to touch or pressure. There is currently no treatment for MCV infection, although Dr. Moore said that identifying the agent and understanding how it instigates cancer formation could lead to targeted interventions.