P&S Journal: Fall 1997, Vol.17, No.3
Researchers Identify Gene Involved in Brain, Breast, Prostate Cancers
Researchers at P&S, in collaboration with Cold Spring Harbor Laboratory, identified a new tumor suppressor gene, known as P-TEN, involved in a large percentage of brain, breast, and prostate cancers. The new tumor suppressor gene is one of more than a dozen known to be involved in a large variety of cancers.
The finding was reported in a March issue of Science. Senior author was Dr. Ramon Parsons, assistant professor of pathology and of medicine in the Herbert Irving Comprehensive Cancer Center. He made the finding with Dr. Michael Wigler of Cold Spring Harbor Laboratory.
"Although initially mutated in breast cancer, mutations of P-TEN were also found in brain and prostate cancer and we expect to find mutations in other cancers as well," says Dr. Parsons. Unlike mutations of genes such as hMSH2 and BRCA1, which are found in hereditary predispositions to cancer, most P-TEN mutations are found in the more common sporadic cancers. More than 80 percent of all cases of cancer are sporadic.
"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," says Dr. Richard Klausner, director of the National Cancer Institute.
Some evidence suggests that loss of P-TEN affects the way a benign tumor becomes malignant. "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." Although this discovery shows great promise, Dr. Parsons cautions that it is not likely to have an impact on patient care for many years.
P-TEN is located on chromosome 10. The role of this chromosome in the development of various sporadic cancers has been investigated for nearly a decade. For instance, scientists believe 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. "This will add a great deal of understanding to the picture of the genetic disarray that takes place when a cell becomes cancerous," says co-author Dr. Wigler.
The study was funded by P&S, Cold Spring Harbor Laboratory, the James S. McDonnell Foundation, the National Cancer Institute, the Department of the Army, Amplicon Corporation, and "1 in 9," a breast cancer advocacy group.