The Mystery of TP53 Unraveled

Mutations within a person’s DNA is one of the most common causes of cancer. p53 is one of the most commonly mutated genes among cancer patients and is a tumor-suppressor that works to regulate cell division and prevent cells from reproducing too quickly. However, when the DNA is mutated, the gene can lose this function and allow cells to grow out of control. Mutations in p53 are found in almost every kind of cancer, including lung, ovarian and laryngeal, among others.

For years, this mutation has intrigued scientists, as the DNA changes can occur at over 1,100 sites within the gene, though there are places, called “hot spots,” where mutations most frequently occur.

A recent study published in Nature Genetics by researchers from the Dana-Farber Cancer Institute, the Broad Institute of MIT and Harvard, and others, found that hotspot mutations are not more likely to produce cancer than mutations at other points within the genetic code.

The study used the newest technology available to create a library of all possible variants of the p53 gene — 8,258 in total. After sequencing the genes, researchers compared hot spot mutations to others and found that they were no more likely to promote cancer than mutations in other locations. They concluded that the tendency of mutations to occur in those locations is due to the way mutations occur and which parts of the body are exposed to carcinogens.

“This indicates we’re correct that mutations in p53 are focused on certain hot spots because those spots are targeted by the specific carcinogens to which cells are exposed,” said William Hahn of Dana-Farber in an interview. Hahn was the senior author of the study and serves as the deputy scientific officer at Dana-Farber.

Understanding the role gene mutation plays in causing cancer is imperative as gene sequencing becomes more common in cancer treatment.