Mayo Clinic researchers reveal treasure trove of genes in kidney cancer

Volume 3, Issue 4, 2014

Summary

This discovery may help lead the way to new treatment options for a rare cancer.

Photograph of John A. Copland III, Ph.D.

John A. Copland III, Ph.D.

Photograph of Han W. Tun, M.D.

Han W. Tun, M.D.

A genomic analysis of clear cell renal cell carcinoma (ccRCC) has uncovered 31 genes that are key to the development, growth and spread of this type of kidney cancer, say researchers from the Mayo Clinic Cancer Center in Florida.

Eight of these genes had not previously been linked to kidney cancer, and six other genes were never known to be involved in any form of cancer.

Their study, published in the June 12, 2014, issue of the journal Oncotarget, is the most extensive analysis to date of the role of gene expression in ccRCC tumor growth and metastasis.

Clear cell renal cell carcinoma is the most common form of kidney cancer.

As part of the study, overexpressed genes were functionally tested in kidney cancer cells to ensure that they were important to some aspect of the cancer process.

"The power of this study is that we looked at genes discovered to be overexpressed in patients' tumors and determined their function in kidney cancer, which has not been done on a large scale before," said the study's senior investigator, Mayo Clinic Cancer Center molecular biologist John A. Copland III, Ph.D. "This is a seminal step in identifying key pathways and molecules involved in kidney cancer so that specific therapies that target these new genes can be developed."

The findings represent a major advancement in therapeutic target identification for clear cell renal cell carcinoma and open new avenues for drug discovery and development, said co-author and Mayo Clinic Cancer Center oncologist Han W. Tun, M.D. "Novel therapeutic agents acting on these new targets should bring about a significant improvement in the prognosis of ccRCC patients."

The research team, which includes Mayo Clinic graduate student and lead author Christina Von Roemeling, has already published several studies identifying some of the genes they discovered in the genetic analysis. In considering the importance of these discoveries to patients, they decided to publish all the genes at once in Oncotarget.

"We are releasing these discoveries to the scientific community so that a large effort can be mounted to find out more about these genes and how they can be effectively targeted," Dr. Copland explained.

The researchers examined an equal number of samples of normal kidney tissues and kidney cancer tissues. They looked at overexpression and underexpression of RNA from the samples and protein production because genes express RNA to produce protein. They found almost 6,000 genes that fit that description.

The researchers then isolated and tested 195 genes that are consistently elevated across patient samples. They then narrowed the list to 31 after testing each in living cancer cells to see if these genes contributed to either growth or spread of the tumor.

"We also found genes with other functions that are key to kidney cancer survival, such as inflammation," Von Roemeling said. "Another found gene is linked to angiogenesis, the production of new blood vessels to support a tumor. It is particularly important because ccRCC is well-known for being a very angiogenic cancer.

"These genes could also serve as biomarkers for accurate diagnosis," Von Roemeling said. "It really is a treasure trove for future research on kidney cancer."

Watch a video of Dr. Copland and Von Roemeling discussing this study.