Newly Discovered Virus Linked to Neuroendocrine Cancer of the Skin

Allison Gandey

January 18, 2008

January 18, 2008 — Researchers are unveiling a new virus in a report published online January 17 in Science. Dubbed the Merkel cell polyomavirus, it is the first to be strongly associated with a human tumor. Polyomaviruses have been shown to cause cancers in animals, but it is unclear what role, if any, they play in human cancer development. Although the important finding does not prove that the polyomavirus causes neuroendocrine cancer of the skin — also known as Merkel cell carcinoma — if confirmed, it might offer clues for future cancer treatment and prevention options.

Merkel cell carcinoma is a rare but extremely aggressive cancer that tends to spread rapidly. The incidence of this skin cancer has reportedly tripled over the past 20 years, to about 1500 cases a year. It tends to be seen in the elderly and in those with compromised immune systems, such as those with AIDS or patients taking transplant-related immunosuppressant drugs. About half of those with advanced Merkel cell carcinoma live 9 months or less.

"If these findings are confirmed, we can look at how this new virus contributes to a very bad cancer with high mortality and, just as important, use it as a model to understand how cancers occur and the cell pathways that are targeted," senior author Patrick Moore, MD, from the University of Pittsburgh School of Medicine, in Pennsylvania, said in a news release. "Information that we gain could possibly lead to a blood test or vaccine that improves disease management and aids in prevention."

Dr. Moore and his wife also discovered the cause of Kaposi's sarcoma. In 1993, the couple identified Kaposi's sarcoma–associated herpesvirus, the most common malignancy in AIDS patients and the most prevalent cancer in Africa.

During an interview with Medscape Oncology, Dr. Moore said his team was surprised by this latest finding. "We were certainly taken aback," he said. "I think anyone uncovering what could be a cause of cancer would be surprised by the finding," he laughed. A lot of work remains, but the Merkel cell polyomavirus might be an exciting clue.

Possible Cause of Rare Cancer Identified

Vaccines are now available against other causes of cancer, such as the human papillomavirus linked to cervical cancer. "The Merkel cell polyomavirus is another model that may increase our understanding of how cancers arise, with possibly important implications for nonviral cancers like prostate or breast cancer," coauthor Yuan Chang, MD, also from the University of Pittsburgh, pointed out in a news release.

Merkel cell polyomavirus, like the human papillomavirus, is said to integrate into the tumor cell genome, but not the genome of healthy cells. This integration destroys the virus's ability to replicate normally and might be the first step toward cancer.

Using a technique called digital transcriptome subtraction, the investigators looked at close to 400,000 messenger ribonucleic acid genetic sequences from 4 samples of Merkel cell carcinoma tumor tissue. They compared the sequences expressed by the tumor genome to gene sequences mapped by the Human Genome Project and systematically subtracted known human sequences to identify a group of genetic transcripts that might be from a foreign organism.

They found that 1 sequence was similar to, but distinct from, all known viruses. The team went on to show that this sequence belonged to a new polyomavirus present in 8 of 10 Merkel cell tumors they tested, but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues.

"This is a rare cancer so it's hard to get enough tissue samples for large studies from just 1 center," Dr. Moore told Medscape Oncology. The group plans to continue collecting samples and will partner with others.

Even if the Merkel cell polyomavirus is proven to play a role inneuroendocrine cancer of the skin, Dr. Chang cautions that the virus is likely to be just part of a much larger picture.

"Now we need to find out how it works," she explained in a news release. "Once the virus integrates, it could express an oncoprotein, or it could knock out a gene that suppresses tumor growth. Either way, the results are bound to be interesting."

The researchers have disclosed no relevant financial relationships.

Science. Published online January 17, 2008.


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