GUMC researchers find gene function 'lost' in melanoma and gl...( PTPRD produces a receptor protein ty...)

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 other words, it changes the activity of proteins either by activating or deactivating them, Waldman says.

"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, Waldman says.

Deletions of PTPRD in human cancer cells were first discovered in 2005, and since then, deletions or mutations of the gene have been discovered in several cancer types, including those of the colon and lung.

In this study, Waldman and his research team, which includes investigators from the National Cancer Institute, the University of Iowa and Duke University, used a laboratory technique known as copy number analysis to look for PTPRD in melanoma cell lines and in samples of human glioblastoma multiforme, the deadliest of brain cancers.

This technique uses a gene microarray that contains millions of probes that can stick to different regions of the human genome. The researchers purified DNA from tumors and then used the microarray chip to quantify genomic copy number. They found that PTPRD was deleted or mutated in 12 percent of melanoma tumors and in 14 percent of glioblastoma tumors examined. "That makes PTPRD one of the most commonly mutated genes discovered yet in melanoma," Waldman says.

"Before this study, no single tyrosine phosphatase was thought to play a generally important role as a tumor suppressor gene n multiple tumor types
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