Scientists have discovered a previously unknown virus and
strongly linked it with the most aggressive form of skin cancer,
they reported in a scientific journal on Thursday.
The cancer, Merkel cell carcinoma, tends to occur most often on
the sun-exposed areas of the body like the face, the head and the
neck. Although it is rare, its incidence tripled from 1986 to
2001, and it now accounts for an estimated 1,200 cases in this
country each year, the National Cancer Institute says.
The virus was discovered by a University of Pittsburgh team that
includes Dr. Patrick S. Moore and his wife, Dr. Yuan Chang. In
1994, when they were at Columbia University, Dr. Moore and Dr.
Chang discovered human herpes virus 8, which causes Kaposi's
sarcoma, the most common malignancy in AIDS patients.
Until the advent of transplant surgery and AIDS, Kaposi's sarcoma
and Merkel cell carcinoma typically affected people older than
65. Now those people have been joined as the most frequent
Kaposi's and Merkel cell sufferers by those whose immune systems
have been compromised by AIDS or organ transplant drugs.
The newly discovered virus belongs to the polyoma family, which
scientists have studied for more than 50 years because other
members of the family have been found to produce cancers in
animals. Although polyoma viruses have been suspected of causing
human cancers, conclusive proof has been lacking.
The Pittsburgh scientists call the new virus Merkel cell polyoma
virus. In a report published online by the journal Science, they
said that while they suspected that it caused Merkel cell skin
cancer, more work was needed to prove it.
"We can say we have a culprit with the smoking gun at the scene
of the crime, but that still doesn't mean he's guilty," Dr. Moore
said in a telephone interview.
"We have a long way to go to prove that this agent is really the
cause," he said. "But the fact that the virus is so strongly
associated with the tumor is at least a very good bet that it is
playing an important role."
Dr. Anthony S. Fauci, director of the National Institute of
Allergy and Infectious Diseases, called the findings "very
interesting and important."
"It is not every day," Dr. Fauci said, "that you have some pretty
compelling molecular proof that a virus is associated, likely
causally, with development of a particular cancerous process."
The polyoma virus is the seventh virus linked to human cancers,
Dr. Moore and Dr. Fauci said. The others, in addition to the
Kaposi's sarcoma virus, are hepatitis B and C viruses, linked to
liver cancer; papilloma virus, to cervical cancer; Epstein-Barr
virus, to cancer of the nose and pharynx and to Burkitt's
lymphoma; and HTLV-1, or human T-cell leukemia virus 1.
While Dr. Moore and Dr. Chang were at Columbia they began
developing a technique called digital transcriptome subtraction,
which they continued to use after moving to Pittsburgh in 2002 to
seek new or known viruses in immune-related cancers.
But finding no tissue samples of Merkel cell carcinoma available
at the University of Pittsburgh, they had to obtain the tissues
from the Comprehensive Human Tissue Network, a nationwide tissue
bank financed by the National Institutes of Health for research
purposes.
The team, which also includes Huichen Feng and Masahiro Shuda,
adapted its technique to benefit from developments like the human
genome project.
"It took us a long time, and we made every mistake we could
possibly make on this," Dr. Moore said.
The researchers found the polyoma virus in the cancers of 8 of
the 10 Merkel patients whose tissues they tested. They also found
that the virus integrated into the genome of the tumor cell, a
discovery strengthening the belief that it plays an important
role in the cancer's cause.
For control purposes, the scientists also tested for the virus
among two groups of people without Merkel cell carcinoma.
Evidence of the new virus was found in tissues from various body
sites in 5 of the 59 people who made up one control group. Such
evidence was also found in skin tissues of 4 of the 25 people in
the second group, some of whom had healthy immune systems, others
impaired.
The findings raise new scientific challenges. One is to determine
any links between the virus and other diseases. Among this team's
next steps is an effort to determine whether a virus is related
to Hodgkin's and non-Hodgkin's lymphoma, Dr. Moore said.
The technique used to identify the Merkel cell polyoma virus
eliminates known human molecular sequences from a sample of
tissue, leaving unknown or nonhuman sequences that the scientists
explore in seeking a possible infectious agent. Dr. Moore said he
hoped the technique would be useful in screening tissues from
patients with diseases of unknown cause to find a new agent or to
reduce the likelihood that they are related to one.
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