TP53 Sequencing and Deletion/Duplication

This test is used to assess the risk of certain cancers and guide follow-up. It detects point mutations, deletions, and duplications in the TP53 gene that are associated with Li Fraumeni syndrome. Li Fraumeni syndrome includes an increased risk for breast, bone, and other cancers, as well as early-onset cancers, including those diagnosed during childhood.

The following individuals may be appropriate for this test:

• Individuals with a personal history of breast cancer diagnosed before the age of 31
• Individuals with a personal history of adrenocortical carcinoma, choroid plexus carcinoma, or rhabdomyosarcoma of embryonal anaplastic subtype
• Individuals with a personal history of a tumor associated with Li Fraumeni syndrome diagnosed before the age of 46, and a family history of tumors associated with Li Fraumeni syndrome
  • Li Fraumeni syndrome associated tumors are:
    • Soft tissue sarcoma
    • Osteosarcoma
    • CNS tumor
    • Breast cancer
    • Adrenocortical carcinoma

Informed consent following genetic counseling is strongly recommended. The person in the family with the earliest diagnosis of a Li Fraumeni syndrome-related cancer should be tested first whenever possible.

You can ask one of our genetic counselors. Please call Quest Genomics Client Services at 866.GENE.INFO to talk with a genetic counselor.

Both women and men with a TP53 gene mutation have a higher risk of cancer. The overall risk of cancer for men is 69% to 95% by age 70. The overall risk for women is 83% to 95% by age 70. Cancer can occur at any age, even in infancy.

The right time is different for every patient. A patient’s current medical status, personal experience with cancer, and general readiness for genetic information all influence the decision to be tested. Having an open dialogue about these topics between healthcare providers and patients can assist with shared decision making.

Patients with a positive result (pathogenic or likely pathogenic mutation detected) have an increased risk for developing certain cancers relative to that of the general population.

The National Comprehensive Cancer Network (NCCN) provides up-to-date surveillance and management recommendations (http://www.nccn.org). Patient referral to an oncology center experienced in treating patients with a hereditary predisposition to cancer may be considered. Such a center can discuss available options with the patient. These options may include increased surveillance and prophylactic surgery. Genetic counseling for family members is advised.

A negative result means that a pathogenic or likely pathogenic mutation was not found in the TP53 gene. Implications of this result depend on the situation:

• Patients previously diagnosed with cancer: The risk of recurrence or a related new cancer is based on the patient’s personal and family histories of cancer. In some instances, it may be appropriate to test for other hereditary forms of cancer. Please call Quest Genomics Client Services at 866.GENE.INFO to discuss possible additional studies with a genetic counselor.
• Patients not previously diagnosed with cancer, but with a family history of cancer: Testing an affected family member is recommended for proper risk assessment. A patient’s risk of cancer is based on his/her personal and family histories of cancer. In some instances, it may be appropriate to test for other hereditary forms of cancer. Please call Quest Genomics Client Services at 866.GENE.INFO to discuss possible additional studies with a genetic counselor.

A VUS result means that the variant has not been previously described in the literature or that the clinical significance is unclear based on currently available evidence. Medical management decisions should be based on personal and family history. Family studies may be indicated to better understand the clinical significance of this variant. If you have questions, please call Quest Genomics Client Services at 866.GENE.INFO to speak with a genetic counselor.