• Test code: 01705
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Li-Fraumeni Syndrome Test

Test description

This test analyzes the TP53 gene, which is associated with Li-Fraumeni syndrome (LFS). LFS causes a significantly increased risk of developing early-onset cancers, including soft tissue sarcoma, osteosarcoma, lung cancer, premenopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemia.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)

Alternative tests to consider

TP53 can also be ordered as part of a larger panel to test for different types of hereditary cancer conditions. Depending on the individual’s clinical and family history, one of these larger panels may be appropriate. Any of these larger panels can be ordered at no additional charge.

  • Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition condition associated with a high risk of developing soft tissue sarcoma, osteosarcoma, lung cancer, premenopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemia. Individuals with LFS will frequently have an earlier onset of these cancers than the general population and may develop multiple primary tumors.

Lifetime cancer risks in Li-Fraumeni syndrome are very high; however, cancer-specific risks are currently unknown. The risk of developing at least one Li-Fraumeni associated cancer is estimated at 50% by age 30 and 90% by age 60.

At least 70% of individuals who have a clinical diagnosis of Li-Fraumeni syndrome have an identifiable pathogenic variant in the TP53 gene.

LFS is inherited in an autosomal dominant pattern. Most affected individuals inherit LFS from a parent. Approximately 7%-20% of cases occur as the result of a spontaneous de novo mutation.

Although its true prevalence is currently unknown, Li-Fraumeni is considered a rare hereditary cancer syndrome.

Li-Fraumeni syndrome testing should be considered in individuals who have all of the following:

  • a sarcoma diagnosed before age 45
  • a first-degree relative with any cancer before age 45
  • a first- or second-degree relative with any cancer before age 45 or a sarcoma at any age

Criteria for evaluating a family for Li-Fraumeni have been established by the National Comprehensive Cancer Network:
For management recommendations, please refer to:

Additional testing and diagnostic criteria for LFS have also been proposed:

  1. Melhem-Bertrandt, A, et al. Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer. 2012; 118(4):908-13. doi: 10.1002/cncr.26377. PMID: 21761402
  2. Gozali, AE, et al. Choroid plexus tumors; management, outcome, and association with the Li-Fraumeni syndrome: the Children's Hospital Los Angeles (CHLA) experience, 1991-2010. Pediatr Blood Cancer. 2012; 58(6):905-9. doi: 10.1002/pbc.23349. PMID: 21990040
  3. Tinat, J, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J. Clin. Oncol. 2009; 27(26):e108-9; author reply e110. doi: 10.1200/JCO.2009.22.7967. PMID: 19652052
  4. Li, FP, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988; 48(18):5358-62. PMID: 3409256
  5. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian Version 3.2019. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2019
  6. Gonzalez, KD, et al. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J. Clin. Oncol. 2009; 27(8):1250-6. doi: 10.1200/JCO.2008.16.6959. PMID: 19204208
  7. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle. PMID: 20301488
  8. Libé, R, Bertherat, J. Molecular genetics of adrenocortical tumours, from familial to sporadic diseases. Eur. J. Endocrinol. 2005; 153(4):477-87. doi: 10.1530/eje.1.02004. PMID: 16189167
  9. Raymond, VM, et al. Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma. J. Clin. Endocrinol. Metab. 2013; 98(1):E119-25. doi: 10.1210/jc.2012-2198. PMID: 23175693
  10. Mouchawar, J, et al. Population-based estimate of the contribution of TP53 mutations to subgroups of early-onset breast cancer: Australian Breast Cancer Family Study. Cancer Res. 2010; 70(12):4795-800. doi: 10.1158/0008-5472.CAN-09-0851. PMID: 20501846

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
TP53* NM_000546.5

TP53: Deletion/duplication analysis covers the promoter region.