A new way of searching for human viruses has helped scientists at the University of Pittsburgh Cancer Institute in the US find a previously unknown one that is linked to a deadly form of skin cancer called Merkel cell carcinoma (MCC). The discovery is published as a paper in this week's publication ahead of print issue of Science and is the result of work by a husband and wife team that had already discovered another virus linked to another incurable skin cancer, Kaposi's sarcoma. The University of Pittsburgh Cancer Institute (UPCI) researchers and authors of the paper, Drs Huichen Feng, Masahiro Shuda, and husband and wife, Drs Patrick Moore and Yuan Chang, describe their 10 year programme to perfect the sequencing technology for hunting the virus, which they have named the Merkel cell polyomavirus (MCV). Their work has not established a causal link between MCV and Merkel cell carcinoma (MCC), but if their results can be confirmed, then they are likely to lead to new treatment and prevention approaches.
The researchers analyzed nearly 400,000 sequences of messenger RNA taken from four tissue samples of MCC tumours using a technique called digital transcriptome subtraction (DTS). The team had developed the DTS method themselves. The DTS system allowed them to compare the tumour gene sequences to those already mapped by the Human Genome Project, so conducting a massive "subtraction" exercise, which left at the end of it, a group of genetic transcripts that were not present in the human genome and could therefore reasonably be assumed to have come from a foreign organism, like a virus. The researchers then mapped the left over genetic transcripts against known viruses and found there was one unknown but distinct sequence. Using this mystery pattern they showed it belonged to a new polyomavirus that was in 80 per cent of the Merkel cell tumours they tested, but only present in 8 per cent of control tissues from various body sites and 16 per cent of control tissues taken from skin.
Merkel cell carcinoma (MCC) is rare but extremely aggressive. It affects about 1.500 Americans a year, and the rate has tripled in the last 20 years. It is more prevalent among AIDS and transplant patients with immune system weakened by treatment with immunosuppressants. MCC starts in subcutaneous cells associated with the sense of touch. It occurs mostly in the face, head and neck and spreads rapidly into other tissues and organs. The life expectancy of a person with MCC is not long. About two thirds of MCC patients die within five years, and about half with the advanced form of the cancer live only nine months or less.
MCV can also be found in healthy people and not just in Merkel cell tumours. As already explained, it behaves like HPV in that it invades and integrates with the DNA of the host cell, and does this before the cell become cancerous. The UPCI team found that 6 of the 8 MCV-positive tumors had DNA patterns that showed viral DNA had integrated with the tumour genome in a way typical of MCV, a monoclonal pattern. This was taken as a strong sign that infection by MCV was the trigger for tumours to start. The researchers repeated these results with other specimens.
"Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma."
Huichen Feng, Masahiro Shuda, Yuan Chang, and Patrick S. Moore.
Science, Published ahead of print, 17 January 2008.
DOI: 10.1126/science.1152586.
skip to main |
skip to sidebar
The Science of Skin Cancer is for patients and physicians who are interested in reading about new developments in the prevention, diagnosis, and treatment of skin cancer. The information in this publication does not constitute medical advice and is not intended to be a substitute for proper medical care provided by a physician.
About Me
- John Hendrix, MD
- John Hendrix, MD has over 17 years experience diagnosing and treating skin cancers. He is a Diplomate of the American Board of Dermatology, a Fellow of the American Academy of Dermatology and a Fellow of the American College of Mohs Surgery.