Li-Fraumeni Syndrome, TP53 Sequencing and Deletion/Duplication

This test is used to identify individuals with Li-Fraumeni syndrome (LFS). It detects single-nucleotide variants, deletions, and duplications in the TP53 gene, which encodes tumor suppressor protein p53. Sample reports and information regarding the specific variants analyzed for each gene are available on our website QuestHereditaryCancer.com.  

If a familial mutation has been detected by sequencing or deletion/duplication studies, the Hereditary Cancer Single Site(s) test [test code 93945] may be considered. Official test results of the family member must be available for laboratory review. For more information, please visit our website QuestHereditaryCancer.com. To discuss a family history with a Quest Diagnostics genetic counselor, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

Generally, this test may be indicated for individualswho meet the Chompret criteria^1,2 summarized below:

• Individual with a tumor from the LFS spectrum (soft tissue sarcoma, osteosarcoma, central nervous system tumor, breast cancer, adrenocortical carcinoma) diagnosed before age 46, and a first- or second-degree relative with a tumor from the LFS spectrum diagnosed before age 56, or
• Individual with multiple primary LFS tumors (except multiple breast tumors), two of which belong to the LFS tumor spectrum with the initial cancer occurring before age 46, or
• Individual with adrenocortical carcinoma, choroid plexus carcinoma, or rhabdomyosarcoma diagnosed at any age, or
• Individual with breast cancer diagnosed before age 31

Informed consent following genetic counseling is strongly recommended.

For more information or to discuss a family history with a Quest genetic counselor, please call
Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

The right time is different for every individual. An individual’s current medical status, personal experience with cancer, treatment or screening plan, and general readiness for genetic information all influence the decision to be tested. Having an open dialogue with individuals about these topics can assist with shared decision-making.

Upon receipt of a fully completed order, our team will verify coverage with your patient’s healthcare insurance plan and estimate their likely out-of-pocket responsibility. If your patient’s estimated responsibility is over $100, we will notify you and/or your patient prior to test initiation to discuss options for continuation or cancellation of the test. Please note that orders lacking complete information will not be processed.

On average, results will be completed 14 to 21 days after receipt of the sample in the laboratory if the family history form and order are complete and the health plan does not require preauthorization. Turnaround time may vary based on delays caused by incomplete orders or insurance authorizations.

Individuals with a positive result have a pathogenic or likely pathogenic variant detected in the TP53 gene and a diagnosis of LFS.¹ A positive result does not mean that an individual has a diagnosis of cancer. Pathogenic and likely pathogenic variants in TP53 have an autosomal dominant pattern of inheritance, meaning that first-degree relatives have a 50% chance to also be positive for this result. Specific risk information will be provided in the result report, and you can visit our website at QuestHereditaryCancer.com for more information.

The National Comprehensive Cancer Network (NCCN^®) provides up-to-date surveillance and management recommendations¹ for individuals with a positive result.

A negative result means that a pathogenic or likely pathogenic variant was not detected in the TP53 gene. For more information regarding specific genetic variants analyzed in this assay please refer to the methods and limitations section of the genetic testing report. Implications of this result depend on the situation:

Individual with previously diagnosed cancer: An individual’s risk of recurrence or a related new cancer is based on their 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 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional studies with a genetic counselor.

Individual without previously diagnosed cancer, but with a family history of cancer: An individual’s risk of tumors or cancer is based on their personal and family histories. Testing an affected family member may further inform this risk assessment. In some instances, it may be appropriate to test for other hereditary forms of cancer. Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional studies with a genetic counselor.

Clinical diagnostic criteria are available if an individual is still suspected of having a diagnosis of LFS in the context of a negative genetic testing result.^2,3

A VUS result means that the variant has not been previously described in the literature or that the clinical significance is unclear based upon currently available evidence. Medical management decisions should be based on personal and family history. Family studies may help to learn more about the clinical significance of this variant. The classification and interpretation of the variant(s) identified reflect the current state of Quest’s understanding at the time of the report. Variant classification and interpretation are subject to professional judgment and may change for a variety of reasons including, but not limited to, updates in classification guidelines and availability of additional scientific and clinical information. It is important to check in with the laboratory annually for variant updates because new information regarding the variant and classification may become available over time. Please visit QuestDiagnostics.com/VariantIQ for information about variant classification. If you have questions, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genetic counselor.