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Team Tracks Genetic Origins of Eye Cancer

A West Virginia University professor and two alumni have tracked the chromosomal abnormalities associated with a tumor that develops in the eye and often leads to blindness and death.// They're hopeful their findings could someday lead to improved treatment for those who suffer from it.

Joginder Nath, professor of genetics and developmental biology, and former doctoral students Jason White ('02) and Alison Director-Myska ('96) published their findings in two recent issues of Cancer Genetics and Cytogenetics.

The first paper, published in July, describes the specific differences in chromosomal material in cell lines established from sample tissue of these tumors. The second, published in the October issue, describes similar anomalies observed in nearly 100 patients.

Both articles reflect research that comprised a large part of White's doctoral research at WVU. Much of the research was conducted at the Armed Forces Institute of Pathology in Rockville, Md., where Director-Myska headed a lab studying chromosomal aberrations.

"Uveal melanoma develops within the eye, and it's commonly detected when vision begins to be affected," White explained. "By this time, the tumor has grown quite large, and it then migrates to the liver. Once this has occurred, the prognosis is quite poor."

Treatment is often aggressive, involving removal of the eye, though more conservative alternatives are being explored and developed.

The WVU team studied these tumors at the chromosomal level. They studied cell lines from tumor tissue samples, and found common rearrangements in chromosomal configurations.

White found these rearrangements using three different techniques: fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and spectral karyotyping (SKY). FISH involves the fluorescent labeling of a piece of DNA to determine where that piece of DNA is found and how many copies there are . CGH is essentially an expanded version of FISH, with entire tumor cell lines, or genomes, labeled in different fluorescent colors, that provides a genome-wide comparison of amplified and deleted regions in DNA. SKY allows the researcher to track the physical rearrangement of chromosomes in a tumor cell, thereby revealing the origins of extra and deleted chromosomal material.

"This research was undertaken with the hope that identification of regions and genes of importance in this disease could lead to improvements in treatment strategies," said Nath, who directs WVU’s interdisciplinary graduate programs in genetics and developmental biology. Nath's research has focused on cytogenetics, the study of chromosomes, throughout his 40-year career.

"While gene therapy has enjoyed limited success to date, knowing the genetic make-up of a given tumor can guide the oncologist toward choosing an appropriate treatment regimen," White explained. "Ideally, this will lead to more preservative therapies, and fewer patients with uveal melanoma will have to endure the loss of their eye."


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