Hereditary Cancer

Li-Fraumeni syndrome (LFS) (p53 gene analysis)

  • Mutation analysis of p53 gene
  • Interrogation for specific mutation (relatives)

Li-Fraumeni Syndrome (LFS) is a rare inherited disorder characterized by autosomal dominant inheritance that greatly increases one's risk of developing cancer during their lifetime. Sometimes people with LFS develop multiple tumors often in childhood or as young adults. In 1969 Dr. Joseph Fraumeni noticed groups of families with a higher number of childhood and adult early onset cancers. With the help of Dr. Frederick Li, they found increased numbers of sarcomas, leukemias, adrenal cancer, and breast cancer in these families than would normally be expected. This “familial cancer syndrome„ ultimately became known as Li-Fraumeni Syndrome. In 1990 researchers found that LFS is most often caused by a mutation in the p53 tumor suppressor gene. When this gene is mutated, it doesn't work properly to stop cell growth and tumors develop.

Cancers associated with LFS include adrenocortical cancer, brain tumors, soft tissue sarcomas, osteosarcomas, breast cancer and leukemia. We now know that numerous other cancers have been seen in LFS families, often occurring at younger ages than expected. Due to the complexity of this disorder it is recommended that patients with LFS seek input from providers experienced in caring for patients with this syndrome.

What causes LFS?

Li Fraumeni Syndrome is caused by a mutation in the p53 tumor suppressor gene. Most people with LFS have a mutation that is passed on from a parent. Occasionally, LFS can result from a new mutation (de novo) without having parents affected or a family history of cancer. Not all families with LFS have a p53 mutation. There are many types of p53 mutations, which can behave differently in every person and within each family. Some families with LFS have very high rates of cancer incidence, while others don't. The degree to which a p53 mutation causes cancer in a family or person is termed “penetrance„.

p53 can function a little bit or not at all depending on the type of mutation to the area of the gene. Every cell has 2 copies of a gene, one from the person's mother and one from the father. The mutated form of p53 is dominant, which means if you have a normal copy of the gene and a mutated form of the gene, you will see the effects of the mutated gene, in this case- a higher risk of developing cancer. If you have 2 normal genes, you will not see the effects. If someone with the mutation has children, they have a 50% chance of passing along the mutation to their children. If you do not have the mutation, you will not pass along the effects to your children.

Genetic analysis

  • A short family history must be taken. Any information regarding the patient's family history is important and quickens the analysis completion.
  • 2 x 3ml of peripheral blood in EDTA anticoagulant are required. The sample is either sent to BioGenomica laboratory on the same day the blood is being drawn, or can be stored for a longer time period in the freezer (-20 °C) until its postage. (Contant us for more information regarding postage details).
  • Genetic reports are handed to the attending physician in less than four (4) calendar weeks.

OMIM* 191170