TP53 Gene, Known Mutation
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 the use in establishing a clinical diagnosis of classic LFS and Li-Fraumeni-like (LFL) syndrome that include the above features listed. 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’s and Eeles’ definitions).
Note: This test is appropriate for predictive testing in families in which a point mutation or small insertion/deletion/duplication has been identified.
SDEL / Single-Gene Large Deletion and Duplication Analysis is appropriate for predictive testing in families in which a large deletion or duplication (whole exon or multi-exon) has been identified.
If a familial mutation has not been previously identified, full analysis of the TP53 gene is more appropriate (P53MS / TP53 Gene, Full Gene Analysis).
Diagnostic testing of individuals with suspected diagnosis of Li-Fraumeni syndrome or Li-Fraumeni-like syndrome when a mutation in the TP53 gene has been identified in an affected family member
Predictive testing of at-risk individuals when a mutation in the TP53 gene has been identified in an affected family member
All detected alterations are evaluated according to ACMG recommendations. Variants are 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
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be performed. If a familial mutation has not been previously identified, order P53MS / TP53 Gene, Full Gene Analysis.
Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with hereditary cancer syndromes.
We strongly recommend that 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.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
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.
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. JNCI. 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 and NM. Lindor. New York, NY, Springer, 2009, pp213-217
3. Li-Fraumeni Syndrome–GeneReviews-NCBI Bookshelf http://www.ncbi.nlm.nih.gov/books/NBK1311/
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