Li-Fraumeni Syndrome (TP53 AMPLIFIED)
Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome,
inherited in an autosomal dominant manner, which can affect both
children and adults.
PrintLi-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome,
inherited in an autosomal dominant manner, which can affect both
children and adults.
It is estimated to occur in approximately 1/20,000 people. Affected individuals are at an increased risk for sarcomas, breast cancer, brain tumors (including astrocytomas, glioblastomas, medulloblastomas and choroid plexus carcinomas), and adrenocortical carcinoma (ACC).
The Ambry Test: TP53 AMPLIFIED offers concurrent gene sequence and deletion/duplication analysis of TP53. Detectable mutations can account for more than 70% LFS cases and 8-22% of LFL cases (clinical sensitivity).
Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome that can affect both children and adults. Estimated to occur in approximately 1/20,000 people and is commonly associated with the following types of cancer: sarcoma (osteosarcoma, or of the soft tissue), pre-menopausal breast cancer, brain tumors (ex. astrocytomas, glioblastomas,medulloblastomas, choroid plexus carcinomas), and adrenocortical carcinoma (ACC).1,2
Clinical criteria consists of:
- Bone or soft tissue sarcoma diagnosed <45 y/o
- A first degree relative (FDR) diagnosed with cancer <45 y/o
- FDR or second degree relative (SDR) diagnosed with any type of cancer <45 y/o or sarcoma at any age
Patients who do not fulfill all of the above criteria, but have been diagnosed with similar cancers before the age of 45 are then categorized to have Li-Fraumeni-Like Syndrome (LFL).1,2
Li-Fraumeni syndrome is caused by mutations in the TP53 tumor suppressor gene. TP53 encodes the p53 protein that activates numerous genes involved in cell cycle arrest, DNA repair, and apoptosis when damaged DNA is present. A deleterious mutation in this gene causes a loss of defensive cellular mechanisms, thus allowing uncontrolled cellular proliferation and tumor progression.4 Individuals with TP53 mutations have a 50% risk of developing any of the associated cancers by age 30 and a lifetime risk up to 90%.2,6 Mutations in TP53 are inherited in an autosomal dominant manner, with an estimated 7-20% of affected individuals being a result of a de novo mutation.1
Studies have shown that a small percentage of women who are negative for BRCA negative are identified to have mutations in TP53.7 Also, individuals with a childhood onset of ACC have a 88% chance of having a mutation in TP53.
Genetic testing can complement clinical findings to enable:
- Confirmation of diagnosis in individuals clinically diagnosed with LFS or LFL
- Appropriate surveillance in TP53 positive patients and their relatives
- Diagnosis of patients with early onset breast cancer who have tested negative for BRCA mutations
- Diagnosis of patients with childhood onset of AC
The Ambry Test: TP53 AMPLIFIED includes concurrent gene sequence analysis and gross deletion/duplication analysis of the TP53 gene. PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 2-11 of the TP53 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and analysis for gross deletions/duplications of the TP53 gene is performed by the Multiplex Ligation-Dependent Probe Amplification (MLPA) kit, developed by MRC Holland. Specific mutation analysis for individual TP53 mutations known to be in the family is also available.
The Ambry Test: TP53 AMPLIFIED is designed and validated to detect approximately >99% of described mutations in TP53 (analytical sensitivity). These detectable mutations can account for more than 70% LFS cases and 8-22% of LFL cases (clinical sensitivity).
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: No
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
Prenatal Testing for those under 18 years of age: Please call one of our Genetic Counselors to discuss your case.
| Test Code | Technique | Days |
|---|---|---|
| 2860 | TP53 Gene Sequence Analysis | 83891x1, 83894x8, 83898x7, 83904x14, 83909x14, 83912x1 |
| 2864 | TP53 Deletion/Duplication Analysis | 83891x1, 83894x1, 83900x1, 83901x10, 83909x1, 83912x1 |
| 2866 | TP53 Sequence and Deletion/Duplication | 83891x1, 83894x8, 83898x7, 83904x14, 83900x1, 83901x10, 83909x15, 83912x2 |
| Technique | Days |
|---|---|
| TP53 Gene Sequence Analysis | 7-21 |
| TP53 Deletion/Duplication Analysis | 7-14 |
| TP53 Sequence and Deletion/Duplication | 7-21 |
1 Gonzalez KD et al. J Clin Oncol. 2009; 27(8): 1250-1256.
2 Birch JM et al. Cancer Research. 1994; 54: 1298-1304.
3 Li FP et al. Cancer Research. 1988; 48: 5358-5362.
4 Levine AJ et al. Cell. 1997; 88: 323-331.
5 Varley JM et al. Human Mutation. 2003; 21: 313-320.
6 Olivier M et al. Cancer Research. 2003; 63: 6643-6650.
7 Walsh T et al. JAMA. 2006; 295(12): 1379-1388.