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Is the p53 Gene More of a Player in Kidney Cancer Than Originally Thought?

By: Hillary Ojeda
Posted: Friday, January 31, 2020

In an effort to understand the true role of the p53 gene in the development of kidney cancer, Haifeng Yang, PhD, of Thomas Jefferson University, Philadelphia, and colleagues focused their attention on PBRM1—the second most mutated gene in kidney cancer. They suggest that PBRM1 may be a “reader” of the activated p53 gene and thus strongly linked to this well-known cancer pathway. Their findings on this genetic scenario, which were published in Nature Communications, may be applicable to other cancers as well.

“This shows us that even though p53 isn’t directly mutated in many kidney cancers, the cancer is still disrupting p53 pathway to drive cancer initiation and growth,” said Dr. Yang in a Thomas Jefferson University press release. “This suggests that there might be a therapeutic window for drugs that activate the p53 pathway, which may preferentially impact PBRM1-defective kidney tumors while sparing normal tissues.”

Using human cancer cell lines and mouse and human tumor samples, the investigators ran a series of biochemical and molecular tests to determine whether PBRM1 could be a translator of the activated p53 gene. They found that PBRM1 employs its bromodomain 4 to bind to the activated p53 gene when the acetyl group is in a certain spot. The event can be disrupted by tumor-derived point mutations in bromodomain 4. If that occurs, mutant PBRM1 will no longer be able to suppress tumor growth.

The study authors plan to determine the therapeutic window and to identify potential drugs to target this genetic pathway. The focus of future research will center on kidney tumor genotypes and which ones might be most likely to respond to treatment.

Disclosure: The study authors reported no conflicts of interest.



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