Asian Scientist (Jun. 27, 2013) – An integrative genomic analysis by Japanese researchers has identified critical genes linked to kidney cancer, paving the way for better treatment of the cancer.
Clear-cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Although ccRCC tumors are often linked to loss of function of the VHL (Von Hippel–Lindau) tumor suppressor gene through mutation or deletion, the genetic causes of the cancer have not been completely uncovered.
Instead of only looking for mutations in ccRCC genomes as other studies have done, the researchers used an integrative strategy that analyzed the ccRCC genome at multiple levels. This was done using a range of high-throughput technologies that analyzed epigenetic changes, DNA mutation, gene expression levels and copy number alterations.
This approach of looking at the kidney cancer genome from many angles allowed the team to fully characterize the genetic factors that contribute to ccRCC.
In their study, published in Nature Genetics, the researchers performed integrative analysis on a total of more than 100 ccRCC cases. They identified several genes, including VHL, that were significantly mutated in most of them as expected.
However, they also identified mutations in some genes that were not previously associated with ccRCC. To confirm if these gene mutations occur frequently in ccRCC, the researchers analyzed another 240 ccRCC tumor samples, looking for mutations in these genes.
Through this analysis, the researchers discovered that mutations in the TCEB1 gene were common in the subgroup of patients that lacked the VHL gene mutation.
According to the researchers, mutations in the TCEB1 gene may interfere with the same tumor suppressive function that VHL is involved in. Therefore, it presents an alternative means by which the tumor may “turn off” the VHL-associated tumor suppression pathway.
By focusing on mutated genes that showed abnormalities in gene expression or number of DNA copies, the researchers were able to identify biological pathways that are significantly altered in ccRCC.
These findings provide valuable insights into the biology of ccRCC, and may one day lead to drugs that target these key cancer pathways.
The article can be found at: Sato et al. (2013) Integrated Molecular Analysis Of Clear-Cell Renal Cell Carcinoma.
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