Li-Fraumeni Syndrome via the TP53 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7521 TP53 81405 81405,81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7521TP5381405 81405, 81479 $540 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Li-Fraumeni syndrome (LFS; OMIM 151623) is a hereditary cancer syndrome that predisposes individuals to multiple neoplasms at an early age. The most common neoplasms associated with LFS are pre-menopausal breast carcinomas, bone and soft-tissue sarcomas, adrenocortical carcinomas, and brain tumors. Although much less common, melanomas, germ cell tumors, gastric carcinomas, and Wilms tumors have also been described in LFS patients (Varley et al. Cancer Res 57:3245-3252, 1997). The average age of malignancy for individuals with LFS is typically between 20 and 45, which is at least two to three decades sooner than is reported for the general population (Nichols et al. Cancer Epidemiol Biomarkers Prev 10:83-87, 2001).

Genetics

Li-Fraumeni syndrome is inherited in an autosomal dominant manner and caused by heterozygous germline variants in the TP53 gene (Malkin et al. Science 250:1233-1238, 1990; Srivastava et al. Nature 348:747-749, 1990). TP53 encodes the well-described cellular tumor p53 antigen (Soussi EMBO Rep 11:822-826, 2010). p53 is a ubiquitously expressed DNA-binding protein that plays a major role in the regulation of cell division, DNA repair, programmed cell death, and metabolism. More than 200 pathogenic variations have been reported throughout the TP53 gene, and nearly all are detectable by DNA sequencing (Human Gene Mutation Database, www.hgmd.cf.ac.uk). Three gross deletions encompassing one or more exons of the TP53 gene have been described, but these account for less than 1% of all LFS patients. The risk of developing cancer for carriers of TP53 variants has been estimated to be ~73% for men and nearly 100% for women (Chompret et al. Br J Cancer 82:1932-1937, 2000).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect pathogenic variants in ~90% of children with an adrenal cortical tumor (Varley et al. Am J Hum Genet 65:995-1006, 1999), ~33% of patients diagnosed with a bone or soft-tissue sarcoma (Toguchida et al. N Engl J Med 326:1301-1308, 1992), 7-20% of patients with multiple primary tumors (Malkin et al. N Engl J Med 326:1309-1315, 1992), and ~7% of women with pre-menopausal breast cancer and a relative diagnosed with a typical LFS cancer (Chompret et al. J Med Genet 38:43-47, 2001). Deletions in the TP53 gene have been detected in 1% of Li-Fraumeni cases (Schneider and Garber. GeneReviews. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the TP53 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

In addition to the regions described above, this testing includes coverage of a region in intron 6 for the detection of a previously documented pathogenic variant (Barel et al. Cancer Genet Cytogenet 103:1-6, 1998).

Indications for Test

This test is recommended for individuals with any childhood cancer, sarcoma, or brain tumor, or an adrenal cortical tumor diagnosed under the age of 45, plus one first or second degree relative with a typical LFS cancer diagnosed at any age and another first or second degree relative diagnosed with any cancer under the age of 60 (Chompret et al. J Med Genet 38:43-47, 2001). Women with pre-menopausal breast cancer and a relative diagnosed with a typical LFS cancer are also candidates for this test. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Gene

Official Gene Symbol OMIM ID
TP53 191170
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Li-Fraumeni Syndrome AD 151623

Related Tests

Name
Breast Cancer - High / Moderate Risk Panel
Breast Cancer - High Risk Panel
Hereditary Breast and Ovarian Cancer - High Risk and Lynch Syndrome Panel
Hereditary Endometrial Cancer Panel

Citations

  • Barel, D., et.al. (1998). "A novel germ-line mutation in the noncoding region of the p53 gene in a Li-Fraumeni family." Cancer Genet Cytogenet 103(1): 1-6. PubMed ID: 9595036
  • Chompret A, Brugières L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, Hua D, Ligot L, Dondon M-G, Bressac-de Paillerets B. 2000. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. British journal of cancer 82: 1932. PubMed ID: 10864200
  • Chompret, A., et.al. (2001). "Sensitivity and predictive value of criteria for p53 germline mutation screening." J Med Genet 38(1): 43-7. PubMed ID: 11332399
  • Human Gene Mutation Database.
  • Malkin, D., et.al. (1992). "Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms." N Engl J Med 326(20): 1309-15. PubMed ID: 1565144
  • Malkin, D., et.al. 1990. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250(4985): 1233-8. PubMed ID: 1978757
  • Nichols KE, Malkin D, Garber JE, Fraumeni JF, Li FP. 2001. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiology Biomarkers & Prevention 10: 83–87. PubMed ID: 11219776
  • Schneider and Garber. GeneReviews. 2010
  • Soussi T. 2010. The history of p53. EMBO reports 11: 822–826. PubMed ID: 20930848
  • Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH. 1990. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348: 747–749. PubMed ID: 2259385
  • Toguchida, J., et.al. (1992). "Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma." N Engl J Med 326(20): 1301-8. PubMed ID: 1565143
  • Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ, Evans DGR, Birch JM. 1997. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer research 57: 3245–3252. PubMed ID: 9242456
  • Varley, J. M., et.al. (1999). "Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors." Am J Hum Genet 65(4): 995-1006. PubMed ID: 10486318

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


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