Li–Fraumeni syndrome heterogeneity

  • P. GargalloEmail author
  • Y. Yáñez
  • V. Segura
  • A. Juan
  • B. Torres
  • J. Balaguer
  • S. Oltra
  • V. Castel
  • A. Cañete
Review Article


Clinical variability is commonly seen in Li–Fraumeni syndrome. Phenotypic heterogeneity is present among different families affected by the same pathogenic variant in TP53 gene and among members of the same family. However, causes of this huge clinical spectrum have not been studied in depth. TP53 type mutation, polymorphic variants in TP53 gene or in TP53-related genes, copy number variations in particular regions, and/or epigenetic deregulation of TP53 expression might be responsible for clinical heterogeneity. In this review, recent advances in the understanding of genetic and epigenetic aspects influencing Li–Fraumeni phenotype are discussed.


Li–Fraumeni syndrome Genotype Phenotype Epigenome Pediatrics 



Li–Fraumeni syndrome




Next-generation sequencing


Copy number variations


Whole-genome sequencing


Compliance with ethical standards

Conflict of interest

The authors declare to have no conflict of interest.

Ethical approval

This work is not a research involving human participants and/or animals.

Informed consent

Not applicable.


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Pediatric OncologyLa Fe HospitalValenciaSpain
  2. 2.Clinical and Translational Oncology Research GroupLa Fe HospitalValenciaSpain
  3. 3.Genetics UnitLa Fe HospitalValenciaSpain
  4. 4.Genetics DepartmentValencia UniversityValenciaSpain

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