Interpretive Handbook

Test 61493 :
TP53 Gene, Full Gene Analysis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome associated with germline mutations in the TP53 (also p53) gene. LFS is predominantly characterized by sarcoma (osteogenic, chrondrosarcoma, rhabdomyosarcoma), young-onset breast cancer, brain cancer (glioblastoma), hematopoietic malignancies, and adrenocortical carcinoma in affected individuals. LFS is highly penetrant; the risk for developing an invasive cancer is 50% by age 30 and 90% by age 70 with many individuals developing multiple primary cancers. Childhood cancers are also frequently observed and typically include soft-tissue sarcomas, adrenocortical tumors, and brain cancer. Other reported malignancies include melanoma, Wilms tumor, kidney tumors, gonadal germ cell tumor, pancreatic cancer, gastric cancer, choroid plexus cancer, colorectal cancer, prostate cancer, endometrial cancer, esophageal cancer, lung cancer, ovarian cancer, and thyroid cancer.


There are published criteria for establishing a clinical diagnosis of classic Li-Fraumeni syndrome and Li-Fraumeni-like (LFL) syndrome that include the features listed above. A larger percentage of families that meet the classic LFS criteria, are predicted to have a detectable mutation within the TP53 gene than families that meet the less strict LFL criteria (Birch and Eeles definitions).

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation of suspected clinical diagnosis of Li-Fraumeni syndrome or Li-Fraumeni-like syndrome


Identification of familial TP53 mutation to allow for predictive testing in family members

Interpretation Provides information to assist in interpretation of the test results

All detected alterations will be evaluated according to the American College of Medical Genetics and Genomics (AMCG) recommendations.(4) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Some individuals who have a diagnosis of Li-Fraumeni syndrome or Li-Fraumeni-like syndrome may have a mutation that is not identified by this method (eg, deep intronic mutations, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of a diagnosis of Li-Fraumeni syndrome or Li-Fraumeni-like syndrome. For predictive testing of asymptomatic individuals, it is important to first document the presence of a TP53 gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


We strongly recommend that asymptomatic patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Predictive testing of an asymptomatic child is not recommended.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant. 


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Lindor NM, McMaster ML, Lindor CJ, et al: Concise Handbook of Familial Cancer Susceptibility Syndromes. Second edition. J Natl Cancer Inst Monogr 2008;(38):1-93

2. Masciari S, Syngal S: The role of p53 in colorectal cancer. In Genetics of Colorectal Cancer. Edited by JD Potter, NM Lindor. 2009, New York, Springer Verlag, 2009, pp 213-217

3. Li-Fraumeni Syndrome-GeneReviews-NCBI Bookshelf. Available at URL:

4. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008;10(4):294-300