Large-scale data mining of gene networks in fruit flies has led researchers to a sensitive and specific diagnostic biomarker for human renal cell carcinoma, the most common type of kidney cancer. In the journal Science, published early online January 22, a team based at the University of Chicago shows that the biomarker known as SPOP is produced by 99 percent of clear cell renal cell carcinomas but not by normal kidney tissue.
Physicians could use SPOP levels to confirm or rule out a diagnosis of renal cell carcinoma (RCC). It could also help them determine the original source of cancers that had spread to other organs from an unknown primary tumor.
"This could serve as a diagnostic tool, lead us to new drug targets and potentially help us detect kidney cancers sooner," said study-director Kevin White, PhD, professor of human genetics, and ecology and evolution, and director of the Institute for Genetics and Systems Biology at the University of Chicago. "It also confirms our strategy of using genomics and systems-level analysis of model organisms such as fruit flies to identify factors that play crucial roles in human disease."
The study began with the fly genome. White and colleagues, who study gene regulationhow genes or entire networks of genes get turned on of offwanted to measure the downstream effects of two key genes, known as Eve and Ftz, that control early steps in the development of flies, beginning just after the eggs are laid.
Because Eve and Ftz regulate the activity of other genes, and many of those genes control the activity of additional genes, both had a large impact. Eve influences the expression of 1,074 different genes and Ftx impacts 1,310 genes.
When they narrowed their search to genes directly impacted, the total fell to 235 genes. About 20 percent of those target genes regulate transcription, the activation of other genes, and 40 percent controlled developmental processes.
|Contact: John Easton|
University of Chicago Medical Center