Li-Fraumeni Syndrome/TP53 Biobank

Description

Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%, with 21% of those cancers occurring by the age of 15 years. There are established guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations. First, with the advent of massively parallel sequencing, increasing numbers of patients are now being identified with a wide range of clinical phenotypes associated with germline TP53 mutations, and the natural history of these patients is less well understood. Second, surveillance for malignancy in LFS and other TP53-associated syndromes involves frequent laboratory and radiologic studies that are imperfect measures of disease onset; therefore, more specific, less invasive biomarker-driven screening methods are needed. Finally, studies to date have not yet identified whether tumors which form in LFS or other germline TP53-associated tumors have unique aberrations or signatures that could be exploited in precision medicine treatment of these patients. In order to study these important issues in LFS, this protocol will establish a TP53 Clinical Database and Biobank. The Investigator plans to use this biobank to study genotype-phenotype correlations in patients with LFS and other germline TP53-associated syndromes, mechanisms of tumor formation, and novel methods of cancer screening in this high risk population.

Conditions

Li-Fraumeni Syndrome, Li-Fraumeni-Like Syndrome

Study Overview

Study Details

Study overview

Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome are cancer predisposition syndromes due to germline aberrations in the TP53 gene. Patients with classical LFS have a lifetime malignancy risk between 80-90%, with 21% of those cancers occurring by the age of 15 years. There are established guidelines for screening patients with LFS that have led to earlier detection and treatment of cancer in this population. There are a number of important issues facing patients identified to have germline TP53 variations. First, with the advent of massively parallel sequencing, increasing numbers of patients are now being identified with a wide range of clinical phenotypes associated with germline TP53 mutations, and the natural history of these patients is less well understood. Second, surveillance for malignancy in LFS and other TP53-associated syndromes involves frequent laboratory and radiologic studies that are imperfect measures of disease onset; therefore, more specific, less invasive biomarker-driven screening methods are needed. Finally, studies to date have not yet identified whether tumors which form in LFS or other germline TP53-associated tumors have unique aberrations or signatures that could be exploited in precision medicine treatment of these patients. In order to study these important issues in LFS, this protocol will establish a TP53 Clinical Database and Biobank. The Investigator plans to use this biobank to study genotype-phenotype correlations in patients with LFS and other germline TP53-associated syndromes, mechanisms of tumor formation, and novel methods of cancer screening in this high risk population.

Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders

Li-Fraumeni Syndrome/TP53 Biobank

Condition
Li-Fraumeni Syndrome
Intervention / Treatment

-

Contacts and Locations

Philadelphia

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 19104

Philadelphia

University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Males or females aged 0 and above.
  • 2. Confirmed germline TP53 mutation or variant. OR Family history of LFS and clinically managed as a LFS patient. OR Meet LFS diagnostic criteria including Classic, Chompret, and LFL (Birch and Eeles) criteria.
  • 3. Informed consent for capable participants. OR Parental/legally authorized representative permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
  • 1. Males or females aged 0 and above.
  • 2. Biological relative of subjects with germline TP53 mutation or variant (LFS), including first degree (siblings, parents) and second degree (grandparents, aunts, uncles) relatives.
  • 3. Negative for germline TP53 mutation or variant.
  • 4. Informed consent for capable participants. OR Parental/legally authorized representative permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
  • 1. Males or females aged 0 and above.
  • 2. Household member of subjects with germline TP53 mutation or variant (LFS), sharing a living space (apartment or free-standing home) for at least 6 months prior to study enrollment.
  • 3. Informed consent for capable participants. OR Parental/legally authorized representative (LAR) permission (informed consent) for pediatric participants or subjects with diminished capacity, and if appropriate, assent.
  • 1. Parents/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  • 2. Known pregnancy at the time of study enrollment.

Ages Eligible for Study

to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Abramson Cancer Center at Penn Medicine,

Kara N Maxwell, MD, PhD, PRINCIPAL_INVESTIGATOR, University of Pennsylvania

Suzanne MacFarland, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital of Philadelphia

Study Record Dates

2029-09-24