Pitt research indicates new virus is culprit, not bystander, in deadly skin cancer

September 23, 2008

University of Pittsburgh scientists are uncovering more evidence that a virus they recently discovered is the cause of Merkel cell carcinoma, an aggressive and deadly form of skin cancer.

The findings, published in this week's early online edition of the Proceedings of the National Academy of Sciences, put to rest the possibility that MCV infects tumors that already have formed. If that were the case, the virus would be a passenger rather than the driver of the disease.

Experiments in human tumors reveal that the cancer develops in two steps: during infection, the Merkel cell polyomavirus, or MCV, integrates into host cell DNA and produces viral proteins that promote cancer formation. Tumors occur when a mutation removes part of a viral protein needed for the virus to reproduce and infect other healthy cells, explained senior investigator, Patrick Moore, M.D., M.P.H, professor of microbiology and molecular genetics at the School of Medicine and director of the Molecular Virology Program at the University of Pittsburgh Cancer Institute. The virus then can spread only as the cancer cells themselves multiply.

Clearly, "MCV infects normal cells before they turn into cancer cells," Dr. Moore noted. "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 two possible reasons why these mutations develop: If viral replication continues, the immune system could recognize the intruder to eliminate diseased cells, or the viral replication itself will lead to the death of the cancer cells. Both of these possibilities provide promising leads to find better ways to kill Merkel cell cancer cells without harming healthy tissues.

Also, "this research shows evolution within tumors on a molecular level," Dr. Moore pointed out. "You can see the specific molecular steps." The team's current work could account for known risk factors for Merkel cell carcinoma such as UV exposure and ionizing radiation, which damage DNA and can lead to the viral mutations.

Merkel cell cancers are rare, occurring in about 1,500 Americans annually. Half of patients who have advanced disease die within nine months of diagnosis, and two-thirds die within two years. The elderly and people with compromised immune systems are at greater risk of developing the cancer, which arises in skin nerve cells that respond to touch or pressure.

In a paper published in Science in January, Dr. Moore and his wife, Dr. Yuan Chang, who co-directs their lab, reported their identification of the virus and that it could be found in 80 percent of Merkel cell tumors. They cautioned that although up to 16 percent of the population carries MCV, very few will develop cancer.

There is no treatment for MCV infection right now, but identifying the agent and understanding how it triggers disease could lead to targeted interventions, Dr. Moore said.

University of Pittsburgh Schools of the Health Sciences

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	Merkel Cell Carcinoma: A Multidisciplinary Approach (Molecular Medicine and Medicinal Chemistry) by Vernon K. Sondak (Author), Jane L. Messina (Author), Jonathan S. Zager (Author), Vernon K. Sondak (Editor), Jane L. Messina (Editor), Jonathan S. Zager (Editor), Ronald C. DeConti (Editor) Merkel cell carcinoma is an uncommon but not rare aggressive cutaneous malignancy. It has many similarities to melanoma, particularly in the need for aggressive multidisciplinary treatment, but far less is known about this disease by most practicing physicians. This book summarizes all of the existing knowledge about Merkel cell carcinoma and provides a much-needed perspective on future opportunities for diagnostic and therapeutic advances. It offers practical "how to" advice on diagnosis, treatment and follow-up, and also insight into how to establish a multidisciplinary Merkel cell carcinoma clinic. In addition, it will serve as a unique resource for trainees (medical students, residents and fellows) as well as for Merkel cell carcinoma patients and their advocates and caregivers. There...
	Merkel Cells, Merkel Cell Carcinoma and Neurobiology of the Skin by Tomomichi Ono (Author), Hiroyuki Suzuki (Author), H. Suzuki (Author), T. Ono (Author), Hiroyuki Suzuki (Editor), Japanese Society for Ultrastructural Cutaneous Biology Symposium 1999 (Editor) Surugadai Nihon Univ. Hospital, Tokyo, Japan. Proceedings of the 1st Symposium of the Japanese Society for Ultrastructural Cutaneous Biology, held in Tokyo, Japan, on November 24-25, 1999.
	Gale Encyclopedia of Cancer: Merkel cell carcinoma by Ed.M. Paul A. Johnson (Author) The article is excerpted from Gale Encyclopedia of Cancer The resource students and researchers will turn to for reliable, up-to-date and clearly written information, the Gale Encyclopedia of Cancer is a comprehensive survey of 120 cancers, cancer drugs, traditional and alternative treatments and diagnostic procedures. The Encyclopedia includes entries covering cancers, cancer drugs, treatments, side effects and diagnostic procedures. Entries typically include the following elements: Causes and Symptoms Definition Description Diagnosis Prevention Resources Risks Special Concerns And more An appendix provides complete contact information for cancer centers, national support groups, government agencies and research groups. Features include anatomical...
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	Merkel cell carcinoma: An entry from Thomson Gale's Gale Encyclopedia of Cancer, 2nd ed. by Paul, Ed.M. Johnson (Author), Rebecca, Ph.D. Frey (Author) Students, researchers, and patients can find reliable, up-to-date and clearly written information in “The Gale Encyclopedia of Cancer,” a comprehensive survey of 120 cancers, cancer drugs, traditional and alternative treatments and diagnostic procedures.