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Gene identified as a new target for treatment of aggressive childhood eye tumor
Date:1/11/2012

New findings from the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project (PCGP) have helped identify the mechanism that makes the childhood eye tumor retinoblastoma so aggressive. The discovery explains why the tumor develops so rapidly while other cancers can take years or even decades to form.

The finding also led investigators to a new treatment target and possible therapy for the rare childhood tumor of the retina, the light-sensing tissue at the back of the eye. The study appears in the January 11 advance online edition of the scientific journal Nature.

Researchers have known for decades that loss of a tumor suppressor gene named RB1 launches retinoblastoma during fetal development. But the other steps involved in the rapid transformation from a normal cell to a malignant tumor cell that occurs in this cancer were unknown.

This study linked the RB1 mutation to abnormal activity of other genes linked to cancer without changing the makeup of the genes themselves. Evidence suggests that epigenetic factors, including reversible chemical changes that influence how genes are switched on and off in tumor cells, are altered when RB1 is mutated.

"The dogma in the field has been that once RB1 is mutated, the genome of the affected cell becomes unstable, chromosomes begin to break and recombine, and mutations quickly develop in the pathways that are essential for cancer progression," said Michael Dyer, Ph.D., member of the St. Jude Department of Developmental Neurobiology and a Howard Hughes Medical Institute Early Career Scientist. "What we found through the Pediatric Cancer Genome Project was exactly the opposite. These tumors contain very few mutations or chromosomal rearrangements."

Dyer is one of the paper's corresponding authors. The others are James Downing, M.D., St. Jude scientific director, and Richard Wilson, Ph.D. director of The Genome Institute at Washington Un
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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