TP53

The TP53 gene provides instructions for making a protein called tumor protein p53. This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way.

Tumor protein p53 is located in the nucleus of cells throughout the body, where it binds directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, tumor protein p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. This process prevents cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.

Because tumor protein p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the "guardian of the genome."

breast cancer - increased risk from variations of the TP53 gene

Changes in the TP53 gene greatly increase the risk of developing breast cancer as part of a rare inherited cancer syndrome called Li-Fraumeni syndrome. These inherited mutations are thought to account for less than 1 percent of all breast cancer cases.

Somatic (noninherited) mutations in the TP53 gene are much more common, occurring in approximately 20 percent to 40 percent of all breast cancer cases. These cancers are typically not inherited and do not occur as part of a cancer syndrome. Many of these mutations change a single protein building block (amino acid) in tumor protein p53. These mutations lead to the production of a nonfunctional version of this protein. The defective protein builds up in cells and cannot regulate cell growth and division.

In some cases of breast cancer, one copy of the TP53 gene is lost and the remaining copy has a mutation that prevents the cell from producing any tumor protein p53. Without this protein, DNA damage accumulates and cells divide in an uncontrolled way, leading to a cancerous tumor. Mutations in the TP53 gene are associated with larger tumors and more advanced disease than breast cancers without TP53 mutations. Recurring tumors are also more likely to have mutations in the TP53 gene.

bladder cancer - associated with the TP53 gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic TP53 mutations in bladder cells have been found in some cases of bladder cancer. Most of these mutations change a single protein building block (amino acid) in tumor protein p53. The altered protein cannot bind to DNA, preventing it from effectively regulating cell growth and division. As a result, DNA damage accumulates in cells. These damaged cells may divide in an uncontrolled way, leading to the growth of a cancerous tumor. Mutations in the TP53 gene may help predict whether bladder cancer will progress and spread to nearby tissues, and whether the disease will recur after treatment.

Li-Fraumeni syndrome - associated with the TP53 gene

Although somatic mutations in the TP53 gene are found in many types of cancer, Li-Fraumeni syndrome appears to be the only inherited cancer syndrome associated with mutations in this gene. More than 60 different mutations in the TP53 gene have been identified in individuals with Li-Fraumeni syndrome. These mutations are typically inherited from a parent and are present in all of the body's cells.

Many of the mutations associated with Li-Fraumeni syndrome change a single protein building block (amino acid) in the part of tumor protein p53 that binds to DNA. Other mutations delete small amounts of DNA from the gene. Mutations in the TP53 gene lead to a version of tumor protein p53 that cannot effectively regulate cell growth and division. Specifically, the altered protein is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to the growth of tumors.

other cancers - associated with the TP53 gene

Noninherited (somatic) mutations in the TP53 gene are the most common genetic changes found in human cancer, occurring in about half of all cancers. For example, TP53 mutations have been identified in several types of brain tumor, colorectal cancer, a type of bone cancer called osteosarcoma, a cancer of muscle tissue called rhabdomyocarcinoma, and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney).

Most TP53 mutations change single protein building blocks (amino acids) in tumor protein p53, which leads to the production of an altered version of the protein that cannot bind effectively to DNA. This defective protein can build up in the nucleus of cells and prevent them from undergoing apoptosis in response to DNA damage. The damaged cells continue to grow and divide in an unregulated way, which can lead to cancerous tumors.