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Li-Fraumeni Syndrome (LFS)

What is Li-Fraumeni Syndrome (LFS)?

Li-Fraumeni Syndrome (LFS) is an inherited familial predisposition to a wide range of certain, often rare, cancers. This is due to a mutation in a tumor suppressor gene known as TP53. 

Children and young adults are susceptible to developing several multiple cancers, most notably soft-tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinoma and acute leukemia. 

Other cancers seen in LFS patients include gastrointestinal cancers and cancers of the lung, kidney, thyroid, and skin, as well as in gonadal organs (ovarian, testicular, and prostate).

What causes Li-Fraumeni Syndrome (LFS)?

Li-Fraumeni syndrome is caused by changes in a gene known as TP53. Genes carry important information that tell our body’s cells how to function. The TP53 gene controls how cells grow and divide. 

One of its main jobs is to prevent cancers from forming. Normally, your cells carry two working copies of TP53. One is inherited from your mother and one from your father. Cells from people with Li-Fraumeni syndrome carry one working copy of TP53 and one copy that is altered. 

This alteration causes the gene to not work properly and is called a mutation. When the remaining working copy of TP53 becomes damaged within a cell, this can lead to a cancer.

What are the symptoms of Li-Fraumeni Syndrome (LFS)?

LFS may be suspected if someone has a personal or family history of cancers featured in LFS. 

In addition, there are certain rare cancers that are characteristic of the syndrome that should alert clinicians to the potential of a diagnosis of LFS. 

Cancers most closely associated with LFS include:

  • Soft tissue sarcoma
  • Osteosarcoma
  • Breast cancer
  • Brain and CNS tumors (glioma, choroid plexus carcinoma, SHH subtype medulloblastoma, neuroblastoma)
  • Adrenocortical carcinoma 
  • Acute leukemia   

How is Li-Fraumeni Syndrome (LFS) diagnosed?

If doctors or genetic counselors suspect a person has Li-Fraumeni syndrome, diagnostic testing may take place: 

  • A blood sample is collected
  • DNA is isolated from the cells in the sample, and the TP53 gene is checked for possible mutations using a variety of methods such as DNA sequencing. DNA sequencing is when a genetic specialist checks the lettering (spelling) of the two copies of a gene to that of a normal sample. If there are differences, the specialist then decides if they might cause a specific disease, such as Li-Fraumeni syndrome. Please note that other methods may also be used, especially when the results of DNA sequencing are negative or unclear. These other tests look for changes that could affect the TP53 gene but that may not be found by DNA sequencing.
  • If a TP53 mutation is found, a genetic counselor will work with the family to find out if other family members should consider testing for the mutation. The genetic counselor will help the family understand the cancer risks of those with Li-Fraumeni syndrome. The genetic counselor can also help with decisions about prenatal genetic testing.

Are there any treatment options for Li-Fraumeni Syndrome (LFS)?

At this time, there is no standard treatment or cure for LFS or a germline TP53 gene mutation. With some exceptions, cancers in people with LFS are treated the same as for cancers in other patients, but research continues on how to best manage those cancers involved in LFS.  

Where can I find more information on Li-Fraumeni Syndrome (LFS)?

Li-Fraumeni Syndrome (LFS) Articles