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)


TP53: Deletion/duplication analysis covers the promoter region.

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. 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
  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. Li, FP, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988; 48(18):5358-62. PMID: 3409256
  4. 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
  5. 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
  6. 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
  7. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. Accessed September 2015.
  8. 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
  9. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301488
  10. 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

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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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

TP53: Deletion/duplication analysis covers the promoter region.