TP53 Gene Mutations

Li-Fraumeni Syndrome (LFS)




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Additional Information

TP53 gene

Associated Syndrome Name: Li-Fraumeni Syndrome (LFS)

Important Note: The information below applies only to individuals known to have TP53 mutations that are germline in nature (mutations present in all cells of the body). Some TP53 mutations which appear to be germline in nature are actually somatic mutations present in only a subset of blood cells or tissues, or in tumor cells contaminating the sample used for genetic testing. Individuals with somatic TP53 mutations do not have Li-Fraumeni Syndrome, and the information below regarding cancer risks, medical management options and information for family members may not apply.

TP53 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
Female BreastHigh Risk
ColorectalElevated Risk
EndometrialElevated Risk
GastricElevated Risk
MelanomaElevated Risk
OvarianElevated Risk
PancreaticElevated Risk
ProstateElevated Risk
OtherHigh Risk

TP53 gene Overview

Li-Fraumeni Syndrome (LFS) 1, 2, 3
  • Individuals with germline mutations in TP53 have a condition called Li-Fraumeni Syndrome (LFS).
  • Individuals with LFS have a high lifetime cumulative risk for a wide spectrum of cancers and for developing multiple primary tumors. Cancer risk is heavily biased towards younger ages, and individuals with LFS often develop cancer at early ages, with the majority of cancers diagnosed under age 45.
  • The most common cancers diagnosed in patients with LFS are premenopausal female breast cancer, soft tissue and bone sarcomas, adrenocortical carcinoma and brain tumors. However, the risk for a diverse group of other cancers may also be increased as detailed in the Cancer Risk Table below.
  • The overall lifetime cancer risk for women is higher than that for men. This is mostly due to the very high risk for female breast cancer compared with the 12.5% lifetime risk for breast cancer in women in the general population of the United States. Male breast cancer risk is not thought to be increased.
  • When possible, individuals with LFS are advised to avoid therapeutic radiation therapy for the treatment of cancer, as this can increase the likelihood of additional malignancies.
  • Although the risk for cancer in patients with LFS is very high, it may be possible to reduce this risk with appropriate medical management. Guidelines for the management of patients with LFS have been developed by the National Comprehensive Cancer Network (NCCN) and the American Association for Cancer Research (AACR). These are listed below. Since LFS is a rare and complex condition, it is recommended that patients with TP53 mutations and a diagnosis of LFS be managed by a multidisciplinary team with experience in the prevention and treatment of the many malignancies for which these patients are at risk.

TP53 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Overall Cancer Risk (male)To age 54, 5, 6, 714%-22%0.1%
To age 205, 6, 725%-33%0.4%
To age 505, 6, 760%-67%3.4%
To age 705, 6, 779%-95%20.3%
Overall Cancer Risk (female)To age 54, 5, 6, 73%-22%0.1%
To age 205, 6, 715%-20%0.3%
To age 505, 6, 773%-92%5.4%
To age 705, 6, 782%-100%19.2%
Overall Cancer Risk (male and female)Risk for a second primary cancer within 10 years of a first cancer diagnosis650%NA
Female BreastTo age 706, 785%, with a strong tendency towards very young ages of diagnosis - the large majority of cases occurring before age 457.1%
Other - including Adrenocortical Carcinoma, Choroid Plexus Carcinoma, Soft Tissue Sarcoma, Bone Sarcoma, and BrainTo age 801, 3, 4, 6Greatly increased risk, with a strong tendency towards young ages of diagnosis - sometimes in childhoodNA
ColorectalTo age 801, 7, 8Elevated risk, with a strong tendency towards young ages of diagnosis - the median age of diagnosis is estimated to be 413.0%
Other - including non-Melanoma Skin, Lung, Leukemia, Lymphoma, Esophageal, Neuroblastoma, Thyroid, and KidneyTo age 801, 3Elevated riskNA
GastricTo age 803, 4, 6, 7Elevated risk, with a tendency towards young ages of diagnosis.0.6%
OvarianTo age 803, 4, 6, 7Possibly elevated1.0%
PancreaticTo age 803, 4, 6, 7Possibly elevated1%
ProstateTo age 803, 4, 6, 7Possibly elevated10.9%
EndometrialTo age 803, 4, 6, 7Possibly elevated2.4%
MelanomaTo age 803, 4, 6, 7Possibly elevated1.6%

TP53 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
Overall Cancer RiskProvide education about the signs and symptoms of cancer1As neededAs needed
Female BreastBreast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.1, 918 yearsNA
Clinical breast examination1, 920 years, or at the age of the earliest diagnosis in the family if under age 20.Every 6 to 12 months
Breast MRI with contrast and/or mammography with consideration of tomosynthesis1, 9Age 20 for MRI. Age 30 for both MRI and mammography.Annually
Consider risk-reducing mastectomy.1, 9IndividualizedNA
Other including Adrenocortical Carcinoma, Sarcomas, Brain tumors, Leukemia, Lymphoma, and other cancers, especially those for which there is a past diagnosis in the family.Comprehensive physical and neurological examination1, 9From birthEvery 3 to 4 months (from birth to age 18) and every 6 to 12 months from age 18
Whole body MRI, including brain1, 9From birthAnnually
Abdominal and pelvic ultrasound1, 9From birthEvery 3 to 4 months (from birth to age 18) and annually from age 18
ColorectalColonoscopy1, 925 years, or 5 years younger than the earliest colorectal cancer in the family, whichever comes firstEvery 2 to 5 years
GastricUpper endoscopy1, 925 years, or individualized to a younger age based on family historyEvery 2 to 5 years
Other including Ovarian, Endometrial, Prostate and Pancreatic cancer.Comprehensive physical and neurological examination1, 9From birthEvery 3 to 4 months (from birth to age 18) and every 6 to 12 months from age 18
Whole body MRI, including brain1, 9From birthAnnually
MelanomaSkin examination1, 918 yearsAnnually

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the TP53 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Approximately 7%-20% of individuals with LFS have not inherited the TP53 mutation from a parent. In these cases the mutation has developed spontaneously in that individual (a de novo mutation). Once this occurs, the children of that individual are each at 50% risk of inheriting the mutation.3

Since TP53 mutations carry a very high risk for cancer in young children, it is important that consideration be given to the possibility of genetic testing and screening at very young ages.

Parents who are concerned about the possibility of passing on a TP53 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).1


  1. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2020. Dec 4. Available at
  2. Villani A, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016 17:1295-305. PMID: 27501770.
  3. Schneider K, et al. Li-Fraumeni Syndrome. 2019 Nov 21. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from PMID: 20301488.
  4. Bougeard G, et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. J Clin Oncol. 2015 33:2345-52. PMID: 26014290.
  5. Amadou A, et al. Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome. Curr Opin Oncol. 2018 30:23-29. PMID: 29076966.
  6. Mai PL, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 2016 122:3673-3681. PMID: 27496084.
  7. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. (Accessed on 1-2-2017)
  8. Wong P, Vet al. Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology. 2006 130:73-9. PMID: 16401470.
  9. Kratz CP, et al. Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. Clin Cancer Res. 2017 23:e38-e45. PMID: 28572266.
Last Updated on 10-Dec-2020