New research published in the journal Cell Reports sheds light on the role of the TP53 gene in preventing the spread of cancer. The TP53 gene codes tumor protein p53, a tumor suppressor that stops cells from dividing and proliferating too fast. Because of this important capability, many previous studies have looked into the role that TP53 plays in cancer; however, this study is the largest to date, incorporating over 10,000 cancer patients and 32 different kinds of cancer. The research was led by Dr. Larry Donehower, a professor of molecular virology and microbiology at the Baylor College of Medicine in Houston, TX.
Using data from The Cancer Genome Atlas (TCGA), the researchers Dr. Donehower and his colleagues were able to identify four genes that show overexpression in mutant TP53 tumors. They linked these four genes to a patient’s prognosis. Dr. Donehower explains:
"If you have a high expression of those four genes, you have a patient who's more likely to have a bad prognosis [...] Conversely, if that patient has a very low expression of those genes, (s)he's probably going to survive longer and have a good prognosis. It will give you a better picture of how (s)he'll fare than just knowing whether (s)he's mutant for TP53 or not.”
But that’s not the only finding from this study: the researchers also concluded that TP53 mutations are associated with genetic instability and occur more frequently in patients with a poorer outlook. They also determined that over 91% of cancers with TP53 mutations also exhibit the “loss of both functional TP53 alleles," or gene variants. These discoveries are significant to widening the scientific community’s understanding of TP53 and its role in cancer.
The distinction with this study, says Dr. Donehower, was its breadth. "Most studies on TP53focus on one cancer type. Looking at 32 different cancer types, you see that certain patterns hold up regardless of cancer type."
Co-author David Wheeler agrees, elaborating that their findings could help develop more treatments. "Since TP53 is one of the most important gatekeepers in cancer prevention, the better we understand this gene, the better able we will be to understand the basic biology of cancer. That will lead to better therapies."