“What is MCC and MCV?”
MCC is Merkel cell carcinoma, a cancer arising from mechanoreceptor nerve cells in skin responsible for detecting touch and pressure. More information is available at the NCI website. MCV or MCPyV stands for Merkel cell polyomavirus, a small virus related to a group of viruses known to cause cancers in animals. It was discovered as monoclonally integrated in the MCC tumor DNA by our lab in 2008. It is described in the Jan 17, 2008 edition of the Science Express article “Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma” by H. Feng, et al.
“Are all MCC tumors infected with MCV?”
No, about 80% of tumors we tested are positive for this virus. We are still trying to find out the difference between MCV-positive and negative tumors and do not know the answer why most – but not all – MCC have MCV infection.
“Does Merkel cell polyomavirus cause Merkel cell carcinoma?”
A qualified yes. Scientists from around the world have looked at over 500 tumors in over 20 different studies and that show an average 75% infection rate. When present, the virus has a “clonal” pattern in the cancer cells indicating that MCV infected and integrated into the very first cancer cell before it began growing into a tumor. The virus in cancer cells also has tumor-specific mutations that contribute to its ability to initiate cancer. When the virus proteins are inhibited (“knocked down”) in cancer cells in the laboratory, the cancer cells die indicating that they are dependent on the virus for their survival. However, MCV infection alone does not cause MCC and other factors are also required. MCV is a common infection that does not cause any disease in most people. It is clear that MCV is just one factor that contributes to MCC and other factors, like mutations from sun exposure or immunosuppression, appear to also be critical.
“Is Merkel cell carcinoma that is infected with MCV different from Merkel cell carcinoma that is not?”
It is too early to tell. One study has found that MCV-positive MCC patients have a better prognosis and survival rate than those with MCV-negative MCC. This has not been replicated elsewhere and the difference, if real, is likely to be small.
“What is a polyomavirus?”
This Wikipedia page is a good place to start. These viruses were so named because they can form multiple types (“poly”) of cancer (“oma”) in experimental animals. Prior to MCV, there were four known human polyomaviruses called JC virus (JCV), BK virus (BKV), KI virus (KIV) and WU virus (WUV). A fifth virus, SV40, is a monkey polyomavirus that may have infected some humans through contamination in the late 1950s-early 1960s. Although the other human polyomaviruses can cause cancer in animals, MCV is the only polyomavirus that has been shown to cause cancer in humans. They are nonetheless important pathogens causing other diseases, especially among AIDS and transplant patients. MCV is the fifth human polyomavirus. It is very different (genetically distant) from the other human viruses. It is a relatively new virus and there are currently numerous scientific groups (including ours) researching to characterize this virus further. Additional information on MCV is also available on Wikipedia.
“Where can I get a copy of the Science paper and other papers published on MCV by the Chang-Moore Lab?”
The paper can viewed on our publications page.
“If someone gets infected with MCV, will they develop MCC?”
Generally, no. Only a very small portion of people who are infected with MCV eventually develop MCC.
“Is there a treatment for MCV?”
No, but identifying the agent makes it possible that new treatments might be developed.
“Is MCV infectious? Do I have to worry about giving MCC to my family or kids?"
No, MCC tumors do not have an infectious virus. In persons who develop MCC, the virus is mutated and is no longer infectious. There is no reason for isolating a person with MCC or restricting kids or others from an MCC patient.
“Can I get tested for MCV?”
We have developed two tests in our laboratory to examine the presence of MCV in both tumor tissue and blood and are enrolling MCC patients in our studies. One test involves immunostaining of the tumor tissue slides with an antibody we developed in the laboratory against an MCV T antigen protein (CM2B4). The other test analyses and quantifies patient serum for presence of antibodies against MCV outer capsid protein VP1. Please see our patients’ page for more details. The results are not likely to individually benefit the participant and there is no clear data on whether MCV positivity affects cancer outcomes.
“If this is a common infection, why do you think it might play a role in MCC?”
What if it is just a passenger virus that infects everyone, including people with Merkel cell carcinoma, but does not cause MCC? When the virus DNA integrates into human cell DNA, it forms a pattern that can be detected using a technique called Southern hybridization. Each site that the virus integrates into has a different pattern. If the virus integrates into a cell that turns into a cancer, then all daughter cells will have a single pattern. If the virus secondarily infects the tumor multiple times (i.e., it is a passenger virus that grows in the tumor but not the real cause of the tumor), then we expect many different patterns to be present. We call this a clonality assay. We found that 6 of 8 tumors tested have a clonal pattern suggesting that the virus infection occurred before the cell became malignant and therefore it is likely that the virus plays a role in this tumor.
“How does MCV cause MCC in those patients that are positive?”
This is an area of active research. MCV is usually a free-living virus but in rare circumstances, it undergoes mutation and integrates into the host cell DNA. This may be due to UV or other mutagens or by chance. The virus expresses a protein that is likely to be a cancer causing protein (an oncoprotein) but it also may disrupt human genes that normally prevent tumor growth. Other changes (mutations) in the Merkel cell DNA may also be needed before a tumor can arise.
“Is this caused by immunosuppression?”
Immunosuppression clearly plays a role in MCC. MCC occurs more commonly among AIDS, transplant patients and persons with other cancers that might cause immunosuppression. Therefore, therapies to improve immunosuppression (such as antiHIV treatment for AIDS patients) are likely to help fight MCC as well. We do not know why some otherwise healthy individuals develop MCC. In some cases this may be due to declining immunity with age or it may be due to a very focal deficit in immunity. These are also areas that require additional research.
“Are other scientists studying this virus?”
We have deposited the virus sequence in the public databases at NIH called GenBank. The information can be downloaded and used to start experiments to examine the virus. The accession numbers are EU375803 and EU375804.
“Is there something I can do?”
Yes, cancer research funding has been stalled in the United States since 2002 and has not kept up with inflation. If you or a family member is affected by cancer, particularly Merkel cell carcinoma, then you have a very poignant message to give to your congressperson about the need to support all forms of nonmilitary biomedical research in the US, including basic, translational, and applied research. If you have not done so already, write to them and also visit the American Cancer Society Advocacy webpage. You can directly support MCC research through the Al Copeland Foundation, founded to find the causes of and cures for MCC. Also, a Merkel cell carcinoma support group can be found here.
“Should my treatment change if MCC is caused by a virus? Should I stop radiation or chemotherapy?”
No. Regardless of whether or not the virus is present, current therapies have been developed and shown to work best for treatment of this cancer. Please do not change therapy because of this one report. Hopefully, new treatments can be developed from this research but this will take years under the best circumstances. We are just at the very beginning in understanding this virus and its potential role in MCC.