Cancer Research paper establishes deleted PTPRD in 12% of melanoma and 14% of glioblastoma tumors researched.
Researchers have discovered a gene that is turned off in malignant melanoma and glioblastoma multiforme. Protein tyrosine phosphatase receptor type D (PTPRD) was deleted or mutated in 12% of the melanoma tumors and 14% of the glioblastoma tumors that the team examined.
PTPRD gene has recently been found to be inactivated in several other cancers as well, suggesting that it may play a tumor suppressor role in a wide variety of different cancers.
“That makes PTPRD one of the most commonly mutated genes discovered yet in melanoma,” says Todd Waldman, M.D., Ph.D., an associate professor of oncology at Georgetown’s Lombardi Comprehensive Cancer Center.
When the researchers restored production of the gene’s protein in cancer cells that harbored PTPRD deletions or mutations, the tumors stopped growing and initiated apoptosit.
“Before this study, no single tyrosine phosphatase was thought to play a generally important role as a tumor suppressor gene n multiple tumor types,” Dr. Waldman continues. “Now we have provided the first functional evidence that PTPRD is a tumor suppressor gene and potentially an important one at that.”
Using copy number analysis, the scientists also discovered PTPRD mutations in both the blood and in tumors of a patient with multiple kinds of cancers. “This suggests that the gene could be responsible for an inherited predisposition to cancer,” notes Dr. Waldman.
PTPRD produces a receptor protein tyrosine phosphatase that bisects the outer membrane of a cell. The part that protrudes outside the cell body is thought to be involved in helping cells stick to each other to form a tissue as well as in cell-to-cell communication. The part that juts into the cell is an enzyme that removes phosphates from other proteins.
“In the absence of PTPRD, there are as yet unknown proteins floating around inside the cell with more phosphate residues than they should have, and it is a well known fact that the presence of these residues activates cellular growth pathways,” he says. “But it is not yet known which specific proteins PTPRD regulates.”
The findings are published in the December 15 issue of Cancer Research. The research was conducted by scientists from Georgetown University Medical Center, the NCI, the University of Iowa, and Duke University.