An observational study in Li-Fraumeni Syndrome, TP53 Gene Mutation and Hereditary Cancer Syndrome, sponsored by Dana-Farber Cancer Institute. Recruiting at 3 sites in United States. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by Dana-Farber Cancer Institute · Observational
The purpose of this research study is to learn more about variants in the TP53 gene both associated with Li-Fraumeni Syndrome (LFS), a hereditary cancer risk condition, and TP53 variants found in the blood for other reasons (e.g. ACE/CHIP and mosaicism).
This research study looks to enroll as many people with LFS or TP53 gene variants as possible in order to:
Study procedures will include:
It is expected that about 1500 people will take part in this research study. Participants will be in this study until it closes or the participant withdraws consent.
The National Cancer Institute is providing funding for part of this study and is considered a study sponsor. They will require that some of the genetic information be made available to the research community without personal identifying information.
25 studies on the registry are indexed under Li-Fraumeni Syndrome; 15 are open to participants now.
This study's planned enrollment of 1,500 is above the median of 439 across 18 observational studies indexed under Li-Fraumeni Syndrome.
Browse Li-Fraumeni Syndrome studies →Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.
Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Adults and children with a TP53 gene variant identified in blood or saliva
Exclusion Criteria:
Variant in the TP53 gene found on a blood or saliva test, have a relative with a variant in the TP53 gene, or because participant meets genetic testing criteria for Li-Fraumeni Syndrome (LFS) based on personal or family cancer history
Genetic: Data and Specimen Collection
* Provide research team and access to relevant medical records * Answer short questionnaires periodically * Consider consenting to other optional parts of the research such as: * Providing up to 3 tubes (15ml) of blood at or near the time of consent, as approved by treating physician (optional). * Provide a saliva sample (optional). * Provide eyebrow hairs for analysis of DNA from the bulb (15-20 eyebrow plucks) (optional). * Provide permission for obtainment of stored tissue specimens from cancer or pre-cancer surgeries or biopsies from the pathology departments where they have been stored (optional). * Consider inviting relatives to join the study (optional).
Repository of specimens and data
Examine accuracy of family history and the extent to which families meet various published Li-Fraumeni family criteria or assess for de-novo mutations using descriptive statistics. Exact binomial confidence limits for percents will be calculated at 95% coverage. Tests of difference between \>2 groups for binary variables will use the Fisher exact test.
Time frame: 5 years or Study closure
Estimation of Cancer Risks in TP53 mutation carriers
Estimate the frequency in ExAc as a population rate and calculate a standardized risk ratio as the ratio of the prevalence of mutations in a given cancer type compared to that in ExAc. P-values and 95% confidence intervals will be calculated assuming the observed number of mutations follows a Poisson distribution with mean equal to the expected value calculated from the ExAC observed frequency.
Time frame: 5 years or Study closure
Modified segregation analysis
For each dataset, the following analyses will be performed using MENDEL: a) the relative risk (RR) across age groups is assumed to be constant; b) the RR is assumed to be a continuous, piece wise linear function of age which was constant before age 40 years and after age 60 years, and linear between ages 40 and 60 years
Time frame: 5 years or Study closure
Estimation of risk for the more commonly occurring cancers associated with inherited TP53 mutations
P-values and 95% confidence intervals will be calculated
Time frame: 5 years or Study closure
Plan to share: Yes — The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting information: Study protocol, Sap, Icf
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Dana-Farber Cancer Institute