CONTACT:    Anita Srikameswaran, SrikamAV@upmc.edu                         Michele D. Baum, BaumMD@upmc.edu PHONE:         (412) 647-3555 FOR IMMEDIATE RELEASE PITT RESEARCH INDICATES NEW VIRUS IS CULPRIT, NOT BYSTANDER, IN DEADLY SKIN CANCER Findings show molecular evolution of virus; reported in Proceedings of the National Academy of Sciences PITTSBURGH, Sept. 22 – 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.  Co-authors of the study are Masahiro Shuda, Ph.D., Huichen Feng, Ph.D., Hyun Jin Kwun, Ph.D., Ole Gjoerup, Ph.D., and Yuan Chang, M.D., all of the Molecular Virology Program at the University of Pittsburgh; and Steven T. Rosen, M.D., of Northwestern University.  Funding for this research was provided by a grant from the University of Pittsburgh EXPLORER fund.  The University of Pittsburgh School of Medicine is one of the nation’s leading medical schools, renowned for its curriculum that emphasizes both the science and humanity of medicine and its remarkable growth in National Institutes of Health (NIH) grant support, which has more than doubled since 1998. For fiscal year 2006, the University ranked sixth out of more than 3,000 entities receiving NIH support with respect to the research grants awarded to its faculty. As one of the university’s six Schools of the Health Sciences, the School of Medicine is the academic partner to the University of Pittsburgh Medical Center. Their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. #  #  # http://www.upmc.com/mediarelations   If you would rather not receive future email messages from University of Pittsburgh Medical Center, let us know by clicking here. University of Pittsburgh Medical Center, 200 Lothrop Street Forbes Tower, Room 8044, Pittsburgh, PA 15213 United States

Excerpt from Wikipedia:

 Merkel cell cancer, also called Merkel cell carcinoma, trabecular cancer, Apudoma of skin, or Small cell neuroepithelial tumor of the skin, is a rare and highly aggressive cancer where malignant cancer cells develop on or just beneath the skin and in hair follicles. This cancer is a type of neuroendocrine tumor, like small cell lung cancer. Once it has metastasized to the lymph nodes, the 5-year survival rate for a patient is about 50 percent. A small tumor (less than 2 cm) that has not metastasized to the lymph nodes reported a 5-year survival rate of more than 90 percent; however, at the time of diagnosis of MCC the 5-year survival was 64 percent. Up to half of patients suffer a recurrence.^[1]

It occurs most often on the face, head, and neck. It usually appears as firm, painless, nodules, or tumors. These flesh-colored, red, or blue tumors vary in size from 5 mm (less than a quarter of an inch) to more than 5cm (2 inches). The tumor grows rapidly. About half of all Merkel cell cancers occur on the sun-exposed areas of the head and neck, while one-third begin on the legs, and 15% occur on the arms. The cancer may also begin on other parts of the body, such as the trunk.

From initial onset, Merkel cell cancer metastasizes quickly and spreads to other parts of the body, tending towards the regional lymph nodes. The tumor tends to invade underlying subcutaneous fat, fascia, and muscle. It can also metastasize to the liver, lungs, brain or bones.

More information can be found on the following links:

http://en.wikipedia.org/wiki/Merkel_cell_carcinoma