L-R: Pat Moore, Yuan Chang, Huichen Feng, Masa Shuda
L-R: Pat Moore, Yuan Chang, Huichen Feng, Masa Shuda
Merkel cell carcinoma (MCC) is an aggressive neoplasm which predominantly involves the skin, but can subsequently metastasize to lymph nodes and other organs. These tumors are thought to arise from neuroendocrine derived mechanorecoptor Merkel cells located at the dermal-epidermal junction. MCC is rare in the general population but appears to be more frequently seen in individuals with advanced age or immunosuppression. The latter underlies the increased risk for MCC in patients who are HIV infected, receiving treatment for transplantation, or have other cancers. The face and the extremities are the most common location for MCC where it appears as nodular, violaceous lesions. Microscopically, the tumor consists of monomorphic cells with scanty cytoplasm and round, regular nuclei. Mitotic activity is prominent and underscores the clinical aggressiveness of this disease.
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 and through the Merkel cell carcinoma patient support group
MCV or MCPyV stands for Merkel cell polyomavirus, a small virus related to a group of viruses known to cause cancers in animals. 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.
It is too early to tell. This work must be repeated by other scientists. There are other factors that are likely to contribute to MCC as well, such as UV exposure and immune suppression. But, the finding that this virus is inserted into the genome of MCC in a monoclonal pattern makes it likely to play a role in this cancer.
Merkel cell carcinoma skin biopsy [Show enlarged]
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.
The Wikipedia link is currently accurate (Jan. 8 2008) although brief. It is a good place to get started. 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. None of these viruses have been proven to cause human cancer although scientists are still investigating the possibility that they also play roles in human cancers. They are nonetheless important pathogens causing other diseases, especially among AIDS and transplant patients.
MCV (not to be confused with molluscum contagiosum virus or murine cytomegalovirus, which are different viruses) is the fifth human polyomavirus. It is the most different (genetically distant) from other human viruses. It is newly discovered so there is no reliable information on it other than the Science paper at this time.
If you have a subscription to Science, you can download the PDF from this link. The abstract can be viewed via this link; we will try to post a link here once the complete article is publicly available.
Generally, no. Only a very small portion of people who are infected with MCV eventually develop MCC.
No, but identifying the agent makes it possible that new treatments might be developed.
No, in general MCC tumors do not have infectious virus. There is much that we do not know about MCV but even in our early studies we find the virus to be a relatively common infection. 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.
No, not currently (2008). It is a new virus and it will take time before tests for it can be developed. As part of this work, we are performing research studies to develop these tests and will be enrolling MCC patients in our studies. The results are not likely to individually benefit the participant and there is no data on whether MCV positivity affects cancer outcomes.
Yes, cancer research funding has been stalled in the United States since 2002 and has not kept up with inflation. Scientists are literally running out of money and leaving research altogether. On average, scientists have to write 8 to 10 grants to have a single one funded, meaning that they are primarily writing for grants rather than doing research. This is particularly alarming since, for the first time in human history, the human genome has been deciphered, and we can now begin to identify the fundamental causes of many different cancers.
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
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.
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 monoclonality assay. We found that 6 of 8 tumors tested have a monoclonal 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.
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.
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.
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.