MONDAY, June 10, 2002 (HealthDayNews) -- Two-thirds of the most serious form of skin cancer have mutations in a gene that also crops up, though less frequently, in many other types of tumors.
A team led by British scientists has found that mutations in the gene, called BRAF, are a common feature of certain tumors and are especially prevalent in malignant melanomas, the deadliest form of skin cancer.
BRAF (pronounced be-raff) codes for an enzyme in a family of proteins called kinases, which play a key role in regulating cell growth and activity. Glitches in the gene can lead to overproduction of the kinase, and, in turn, unchecked cell growth, a signature of tumors.
"The most exciting thing about this discovery is that it could be a direct lead to new treatments for malignant melanoma," Dr. Michael Stratton, a researcher with the Wellcome Trust Sanger Institute in Hinxton, U.K. and a co-author of the study, said in a statement. "Because mutated BRAF is permanently stuck in the 'on' position, we have already started searching for drugs that will switch it back off. These drugs would be expected to stop the growth of these cancers."
Melanomas make up only about 4 percent of skin cancer cases, but they account for nearly eight in 10 deaths from the disease, according to the American Cancer Society. The cancer group estimates that 53,600 cases of melanoma will be diagnosed in this country this year, and 7,400 people will die of the disease.
The incidence of melanoma in industrial nations has been rising faster than that of any other cancer. Since 1973, its mortality rate has climbed 44 percent, the cancer society said.
BRAF, and the kinase it codes for, belong to a chain link of chemicals. At the head of this pathway are a group of genes called RAS, mutations in which have been identified in about 15 percent of human tumors.
But scientists have been puzzled to find that some patients have tumors with normal RAS but an abnormal RAS pathway. The latest work, which appears this week in the online issue of the journal Nature, could help explain why.
Stratton and his colleagues, including researchers in the United States, Europe, Hong Kong, and Australia, looked for potential cancer genes in 15 human tumor lines, which they compared with healthy cells taken from the same patients.
BRAF was a common thread among the various tumors, which included breast, colorectal, ovarian, lung, and skin cancer.
Wooster's group then analyzed nearly 1,000 cancer cell samples to see how frequently the wayward gene appeared. BRAF mutations, and two in particular, turned up most often in melanoma, present in two of every three samples. Eighty percent of the errors involved a single spot in the gene.
They also found BRAF flaws in 14 percent of primary ovarian tumors, 12 percent of primary colorectal cancers, and a smattering of lung and breast cancer samples.
Dr. Barbara Weber, a tumor specialist at the University of Pennsylvania in Philadelphia and a co-author of the study, said the findings don't necessarily mean BRAF mutations cause melanoma or other cancers. But "they clearly are playing an important role," she said.
Because BRAF seems to be vulnerable at a single point, "it's sort of the weak link" in the RAS pathway, said Weber, of the Abramson Family Cancer Research Institute at Penn.
The findings may explain why some tumors don't respond to drugs that inhibit errant RAS when they should: they're really BRAF problems instead. "You wouldn't expect a RAS inhibitor would work if there's no RAS mutation," Weber said. "But targeting that with a BRAF inhibitor might work."
What To Do
To find out more about melanoma, try the Melanoma Patients' Information Page, or MEDLINEplus.
