This document addresses genetic testing for TP53 mutations.

The TP53 gene (also known as p53) located on chromosome 17 is a tumor suppressor gene. The protein product of the TP53 gene binds to cellular DNA and is involved in the control of the cell cycle and apoptosis (programmed cell death).

Note: For additional information on genetic testing for malignant conditions, please refer to:

• CG-GENE-13 Genetic Testing for Inherited Diseases
• CG-GENE-14 Gene Mutation Testing for Cancer Susceptibility and Management
• CG-GENE-15 Genetic Testing for Lynch Syndrome, Familial Adenomatous Polyposis (FAP), Attenuated FAP and MYH-associated Polyposis
• CG-GENE-16 BRCA Genetic Testing
• GENE.00052 Whole Genome Sequencing, Whole Exome Sequencing, Gene Panels, and Molecular Profiling

Clinical Indications

Medically Necessary:

Germline testing for cancer susceptibility

1. TP53 gene mutation testing for Li-Fraumeni syndrome (LFS) is considered medically necessary when any one of criteria A through H and all of criteria I are met:
   1. The individual has a family history of known TP53 mutation; or
   2. The individual was diagnosed with sarcoma prior to age 45 years; and
      1. Has a first-degree relative who was diagnosed with cancer prior to age 45 years; and
      2. Has an additional first- or second-degree relative on the same side of the family who was diagnosed with cancer prior to age 45 years, or sarcoma at any age; or
   3. The individual was diagnosed with a tumor from the LFS tumor spectrum (for example, soft tissue sarcoma, osteosarcoma, brain tumor, breast cancer, adrenocortical carcinoma, leukemia, lung bronchoalveolar cancer) prior to age 46 years; and
      1. Has at least one first-or second-degree relative with any of the above LFS spectrum tumors (other than breast cancer, if the proband has breast cancer) diagnosed prior to the age of 56 years or with multiple primaries at any age; or
   4. The individual was diagnosed with multiple tumors (except multiple breast tumors), two of which belong to LFS tumor spectrum, with the initial cancer occurring prior to age 46 years; or
   5. The individual was diagnosed with adrenocortical carcinoma, choroid plexus carcinoma or rhabdomyosarcoma of embryonal anaplastic subtype at any age, regardless of family history; or
   6. The individual was diagnosed with early onset breast cancer at age 30 years or younger; or
   7. The individual has a personal or family history of pediatric hypodiploid acute lymphoblastic leukemia; or
   8. The individual’s somatic tumor testing has identified a TP53 variant and both of the following criteria are met:
      1. Personal and family history suggest a germline mutation; and
      2. The results of germline testing are likely to be used to guide further medical management of the individual;
         and
   9. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.
2. Prenatal or preimplantation genetic testing is considered medically necessary to establish a diagnosis of LFS in the offspring of individuals with known TP53 genetic mutation, and genetic counseling, which encompasses all of the following components, has been performed:
   1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
   2. Education about inheritance, genetic testing, disease management, prevention and resources; and
   3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
   4. Counseling for the psychological aspects of genetic testing.

Somatic tumor testing

TP53 gene mutation testing is considered medically necessary for individuals diagnosed with chronic lymphocytic leukemia or hypodiploid acute lymphocytic leukemia to identify those who would benefit from treatment with chemotherapy.

Not Medically Necessary:

TP53 gene mutation testing is considered not medically necessary in individuals not meeting the criteria above.