Li-Fraumeni Syndrome via the TP53 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
713 TP53$770.00 81405 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
This test is predicted to detect pathogenic mutations 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).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 TP53$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity
Deletions in the TP53 gene have been detected in 1% of Li-Fraumeni cases (Schneider and Garber. GeneReviews. 2010).

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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 2-3 decades sooner than reported for the general population (Nichols et al. Cancer Epidemiol Biomarkers Prev 10:83-87, 2001).
Li-Fraumeni Syndrome is inherited in an autosomal dominant manner and caused by heterozygous germline mutations 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, 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 mutations has been estimated to be ~73% for men and nearly 100% for women (Chompret et al. Br J Cancer 82:1932-1937, 2000).
Testing Strategy
This test involves bidirectional DNA sequencing of the coding exons (2-11) of the TP53 gene, plus ~20 bp of flanking non-coding DNA on either side of each exon. In addition, this test includes the sequencing of a region in intron 6 for the detection of a previously documented pathogenic mutation (Barel et al. Cancer Genet Cytogenet 103:1-6, 1998). We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
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 mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


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


Name Inheritance OMIM ID
Li-Fraumeni Syndrome 151623

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Genetic Counselors
  • Barel, D., (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., (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., (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., 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., (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., (1999). "Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors." Am J Hum Genet 65(4): 995-1006. PubMed ID: 10486318
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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