Dr William Gallagher, UCD School of Biomolecular & Biomedical Science and UCD Conway Institute has led the work of a team of researchers who are trying to identify potential biological markers that could flag aggressive forms of melanoma. Using the latest gene chip technology, their work has focused on 66 genes that undergo changes as a melanoma moves from a non-aggressive to an aggressive state. Dr Gallagher and his team have discovered that a common feature among a significant percentage of these genes is that they have been chemically altered by a process called DNA methylation.

One of these genes turned off by this process, TSPY, is located only on the male Y chromosome and, for the first time, may provide a molecular clue to the commonly held belief that men are not only more likely to develop melanoma but that it tends to be more aggressive.

The Carcinogenesis paper also describes how this group of scientists have slowed tumour growth by treating skin cancer cells with an agent called DAC (2'-deoxy-5-azacytidine), which turned back on the TSPY gene and others in the group of 66 being studied. Commenting on the finding, Dr Gallagher said, DAC is now being evaluated in a wide variety of clinical trials worldwide, with the TSPY gene perhaps being a useful biomarker of treatment for patients receiving this candidate drug.

Dr Gallagher has been working closely on this project with an expert in DNA methylation, Spanish scientist Dr Manel Esteller, Director of the Epigenetics Laboratory at the Spanish National Cancer Center (CNIO).

ucd.ie/conway/

Huntsman Cancer Institute investigators discovered that certain genes contain a special type of nucleosome bearing a protein called Htz1. This Htz1-containing nucleosome was shown to be "fragile," meaning it is ejected from the gene in a regulated manner, allowing reading of the gene's instructions by the cellular machinery. When the gene returns to its inactive or repressed state, the Htz1 nucleosome is reconstructed, again blocking the machinery from reading the gene.

Cairns, an associate professor in the Department of Oncological Sciences at the University of Utah School of Medicine and an investigator with the Howard Hughes Medical Institute, along with Huntsman Cancer Institute graduate students Haiying Zhang and Douglas N. Roberts, studied yeast cells to make the discovery.

"We and hundreds of other laboratories world-wide use yeast as a model system to study gene expression, as the analytical tools for studying yeast are actually more advanced than those available for human cells. However, all the factors that we study in yeast have virtually identical counterparts in human cells, so we fully expect the discovery to apply in humans as well," Cairns says.

hci.utah