Mutations in TP53 Influence Cancer Treatment and Prognosis

Among the many cancer-related genes, TP53 is one of the best studied, known for its tumor suppressor role. It acts as a "sentinel" that monitors abnormal cellular activity, senses cellular stress or damage, and accordingly prevents abnormal cells from dividing or making abnormal cells "kill themselves", thereby preventing damaged cells from multiplying. The p53 protein encoded by TP53 has a tumor suppressor role and is known as the "guardian of the human genome".

When an important role such as TP53 is mutated, it promotes cancer in addition to the failure of an important cell safety mechanism. Understanding the mutation process is important for preventing cancer and developing more effective treatments.

Recently, a study published in the journal Cell Reports by Baylor College of Medicine in the United States has revealed how the TP53 gene is mutated and the role of these mutations in the diagnosis of clinical prospects.

The team, led by Larry Donehower, professor of molecular virology and microbiology at Baylor College of Medicine, studied 10, 225 patient samples from 32 different cancers reported by The Cancer Gene Atlas (TCGA) and compared them with another 80, 000 mutations in a database constructed over the past 30 years by Thierry Soussi, professor of molecular biology at the University of Sorbonne in Paris.

The team found that Tp53 mutations were more frequent in cancer patients with poorer survival rates in all cancer types studied. But researchers have also found a way to predict prognosis more accurately.

Professor Donehower said: "We found four up-regulated genes in mutant TP53 tumors, whose expression was associated with patient outcome. If the expression levels of these four genes are high, then it is possible that patient prognosis is worse; conversely, if the expression of these genes is very low in patients, it is possible that patients will live longer and have a better prognosis. The expression of these genes allows doctors to better understand the future of the patient, not just refer to the patient's TP53 mutation."

At the chromosomal level, the team found a clear pattern of TP53 gene loss. More than 91% of TP53 mutant cancers exhibit second-allele mutation loss, which is caused by mutation, chromosomal deletion, or gene duplication. However, the incidence of gene duplication is much higher than previously thought.

It has also been shown that TP53 mutations are strongly associated with genomic instability, suggesting a role for normal proteins in monitoring chromosomal integrity. In most TP53 mutant tumors, there is increased oncogene amplification as well as profound loss of tumor suppressor genes. Tumors with TP53 mutations differ from non-mutated tumors in RNA, miRNA, and protein expression patterns, and mutated TP53 tumors show enhanced expression of cell cycle progression genes and proteins. In addition, the mutant TP53 RNA expression signature was significantly associated with reduced survival in 11 cancer types. Thus, TP53 mutations have a profound impact on tumor cell genomic structure, expression, and clinical prospects.

Although there are many studies on TP53, this is the first time that five different data collection methods have been used to detect such a large number of tumors and cancer types. Donehower stated that the size of this study allowed his team to notice patterns and correlations brought about by large samples, which may not be apparent in smaller samples.

Collected by Creative BioMart, a recombinant protein provider.