Multiple Genes Discovered Are Key to Kidney Cancer

A genomic analysis of clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, has uncovered 31 genes that are fundamental to the development, growth and spread of the cancer.

The ccRCC kidney cancer is one of the top 10 solid cancers in the USA, and while the prognosis for kidney cancer that has not spread is good, patients with advanced or metastatic cancer will develop drug resistance. Patients with untreated metastatic disease have a five-year overall survival rate of less than 10%.

Scientists at the Mayo Clinic (Jacksonville, FL, USA) purified ribonucleic acid (RNA) samples derived from 72 matched normal and diseased ccRCC patient tissue across all stages of the disease. They looked at over- and under-expression of RNA from the tissue, as well as protein production because genes express RNA to produce protein. They found almost 6,000 genes that fit that description. They isolated and tested 195 genes that are consistently elevated across patient samples.

Gene array expression analysis was performed using Human Genome U133 Plus 2.0 Array chips (Affymetrix; Santa Clara, CA, USA). The team also performed among other techniques real-time quantitative polymerase chain reaction analysis, immunohistochemistry and immunocytochemistry, western blot analysis, and cell-death analysis via flow cytometry. Cell death analysis was performed using an Accuri C6 flow cytometer (BD Biosciences; San Jose, CA, USA) with unstained natural T (NT) cells used to set population parameters. The investigators found eight genes had not been previously linked to kidney cancer, and six other genes that were never known to be involved in any form of cancer.

John A. Copland, PhD, a molecular biologist and the study's senior investigator, said, “The power of this study is that we looked at genes discovered to be over-expressed in patients' tumors and determined their function in kidney cancer, which has not been done on a large scale before. 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 to treat this cancer.” The study was published on June 12, 2014, in the journal Oncotarget.

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