What Causes Merkel Cell Carcinoma?

Although we know some of the things that can increase a person’s risk of Merkel cell carcinoma (MCC), it’s not clear exactly how these things might cause MCC.

Cancer is caused by changes in the DNA inside of cells. DNA in our cells makes up our genes , which control how our cells work. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes help control when our cells grow, divide into new cells, and die:

• Genes that help cells grow, divide, and stay alive are called oncogenes.
• Genes that keep cell growth in check by slowing down cell division or making cells die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in many different genes are usually needed for a cell to become a cancer cell.

Researchers don’t yet know all of the DNA changes that can result in MCC, but they have found that many of these cancers have changes in tumor suppressor genes.

MCC does not seem to run in families, so the DNA changes that lead to MCC are not likely passed on (inherited) from a person’s parents. Instead, these changes probably happen during the person’s life. Sometimes these changes might just be random events that happen inside cells, without having an outside cause. But sometimes the cause might be something specific, like long-term sun exposure or infection with the Merkel cell polyomavirus (MCV).

Ultraviolet (UV) radiation can damage the DNA inside skin cells. Sometimes this damage affects certain genes that control how and when cells grow and divide, which may be the first step on the path to cancer.

How MCV infection plays a role in the development of MCC isn't clear. But researchers have found that the virus can get inside cells and cause them to make a protein that turns off tumor suppressor genes, which might lead to MCC.

MCV infection might help explain why people with weakened immune systems have a higher risk of MCC. It might be that the virus is normally kept in check (but not killed) by the immune system. A weakened immune system could then allow the virus to grow and flourish, which in turn might raise the risk of MCC.

Scientists are looking for the specific DNA changes inside MCC cells to help explain what causes it. A better understanding of how damaged DNA leads to MCC might also be used to design better treatments for it.