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Mayo Clinic researchers find genetic secrets to common kidney cancer
Date:5/18/2010

levels of mRNA for each gene in tissue samples taken from kidneys that were removed from 10 ccRCC patients. The kidneys were removed at the time of surgery and contained both normal tissue as well as tumor, so the scientists compared gene expression between the two to see what genes in the cancer were either over- or under-expressed, compared to normal cells.

Researchers found that 13,729 genes had altered expression in the cancer a figure Dr. Copland calls "just astounding, especially in trying to develop new treatments and in understanding the causes of kidney cancer." They used novel software that grouped these genes into meaningful biological pathways which helped them discover master genes. Each of these master genes regulates hundreds of "downstream" genes.

Researchers confirmed these gene expression findings in 20 kidneys removed from other ccRCC patients. Then, they validated gene expression at the protein level in kidneys taken from a different group of 50 ccRCC patients. To provide biological relevance, researchers then grew live normal kidney and ccRCC cells in a culture mediuam and conducted experiments.

Among the research findings are:

  • The top three biological pathways found included genes regulating normal kidney function and metabolic functions lost in ccRCC. Genes in immune pathways were also over-expressed.
  • A gene expression signature responsible for adipogenesis, which is the accumulation of globules of fat inside cells that is the reason for the "clear" appearance of ccRCC. Using a novel cell culture technique, they turned ccRCC cell lines into fat-acquiring "clear cells," mimicking what happens in patients. In patient-matched normal cells, fat is not produced.
  • The loss of four developmental transcriptional factor genes in ccRCC that are important for normal kidney development. One of these genes, GATA3, controls many genes through transcriptional regulation of cell growth, immune f
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-0746
Mayo Clinic
Source:Eurekalert

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