Above: Dr. Ramon Parsons, assistant professor of pathology and of medicine, who along with fellow researchers at P&S and Cold Spring Harbor Laboratory, identified a new tumor suppressor gene called P-TEN involved in several types of cancer.

Collaborating with researchers at Cold Spring Harbor Laboratory in New York, P&S researchers have identified a new tumor suppressor gene called P-TEN involved in several types of cancer. Dr. Ramon Parsons, assistant professor of pathology and of medicine, made the finding with Dr. Michael Wigler and colleagues at Cold Spring Harbor Laboratory. Their findings were published in the March 28, 1997, issue of Science.

Their theory is that loss of P-TEN paves the way for a benign growth to become a malignant tumor. "We identified 20 mutations of P-TEN in advanced brain, breast, and prostate cancers," says Dr. Parsons. "Based on our finding, it may someday be possible to test people for mutations of P-TEN, which would give an early warning of cancer danger. P-TEN may also allow us to identify drugs to better treat cancer overall." Though the discovery shows great promise, Dr. Parsons cautions that it is not likely to have an impact on patient care for many years. But, he adds, "This is probably the most important tumor suppressor gene since p53, which is involved in almost all cancers."

Dr. Richard L. Klausner, director of the National Cancer Institute in Bethesda, Md., applauded the finding. "Discoveries such as this are rapidly filling in the missing pieces of the cancer puzzle. This discovery represents one of the first genes to be implicated in aggressive and generally fatal brain tumors, a type of cancer in which we desperately need clues that the P-TEN gene may offer."

P-TEN is located on chromosome 10. The role of this chromosome in the development of various sporadic cancers--80 percent of all cancers are of this type, in which a mutation occurs suddenly--has been investigated for nearly a decade. For instance, scientists believe that the mutation that causes Cowden's syndrome, a genetic condition that often leads to breast cancer and other tumors, is located on chromosome 10. P-TEN gets its name from its similarity to phosphatases and to tensin, part of a complex of proteins that sits below the cell surface and which may be involved in the spread of tumors. The similarity between P-TEN and protein phosphatases, which remove phosphates from proteins, is significant because many oncogenes are part of a class called tyrosine kinases, which add phosphates to proteins.

Representational difference analysis (RDA), an advanced genetic technology developed at Cold Spring Harbor Laboratory, played a key role in the identification of the P-TEN gene. RDA analyzes DNA from diseased and normal cells, then subtracts shared sequences, making it easier for the researchers to see the remaining difference. In this case, the researchers used RDA to find unique sequences present in normal tissue but missing in breast cancer. A researcher at the Wigler lab used RDA to obtain the first probe for the P-TEN gene. Researchers at both labs together mapped the probe to chromosome 10. Researchers from the Parsons lab then analyzed the P-TEN gene's mutations.

To learn more about P-TEN, visit http://cpmcnet.columbia.edu/news
/press_releases/03-27-97.html on the World Wide Web.