Li-Fraumeni syndrome - TP53 gene mutation. Everything you need to know.

Li-Fraumeni syndrome (LFS) is rare but may become one of the possible causes of cancer. As an autosomal genetic disorder, it carries a risk of mutations being inherited by the offspring of carriers. This risk is as high as 50%. Li-Fraumeni syndrome was first described in 1969 by American doctors: Frederick Li and Joseph Fraumeni.

LFS is also commonly referred to as hereditary predisposition to cancer, especially breast, colon, brain, and skin cancer.

Causes of Li-Fraumeni syndrome

The main cause of Li-Fraumeni syndrome are abnormalities in the P53 tumor suppressor protein (TP53) gene on chromosome 17p13. Among other things, the TP53 protein is responsible for anticancer mechanisms and plays a role in cellular aging as well as activation of repair proteins during DNA damage. This means that the protein encoded by the TP53 gene decides whether, when DNA damage occurs, it will be repaired or whether the damaged cell will self-destruct.

TP53 mutations do not occur in all carriers however. In about 30% of cases, Li-Fraumeni syndrome can be caused by loss of function of a suppressor gene, leading to the development of cancers of epithelial and non-epithelial origin. Mutation of the gene causes the resulting TP53 protein to fail in its primary function of localizing and destroying cells associated with carcinogenesis.

What are the symptoms?

When to suspect LFS? It is a good idea to go for preventive testing if the factors listed below are present. Additional information can be obtained by learning the family history of cancer. High risk occurs when:

• Two (or more) malignant tumors or cancers in both paired organs have developed,
• Cancer has developed in a person at a very young age,
• Relatives in at least two generations have had cancer,
• Coexistence of neoplasms that are typical for Li-Fraumeni syndrome (e.g., sarcoma and adrenocortical carcinoma) was found.

This means that the symptoms of Li-Fraumeni syndrome are similar to those of numerous cancer types. Among these are:

• Skin changes,
• Significant feeling of weakness and weight loss,
• Pain in the abdomen, lumbar region, chest,
• Prolonged fever,
• Enlarged lymph nodes,
• A palpable lump in the breast,
• Unnaturally long-lasting cough,
• Hemoptysis.

It is important to note that there are no common, typical symptoms of cancer. Symptoms can vary, but the most worrisome are those that persist for more than two weeks, do not go away, or come back. Persistent pain is also an important warning sign that should not be ignored.

Diagnosis and treatment

Prevention of Li-Fraumeni syndrome consists mainly of early genetic cancer diagnosis that appears at a young age. First of all, the very diagnosis of the TP53 gene mutation should prompt increased preventive examinations: MRI, mammography or ultrasound. However, it is important to remember that not every family member diagnosed with an inherited cancer has a mutated TP53 gene. Various genetic diagnostic techniques are used to be sure of carrier status. Tests are carried out from a patient's saliva or venous blood sample, and include analysis of the TP53 coding sequence located on chromosome 17.

Unfortunately, there is currently no known treatment for Li-Fraumeni syndrome. The recommendation is to avoid radiation therapy, CT scans, X-rays, ionizing radiation, and sunlight.