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J Pediatr Genet 2016; 05(02): 084-088
DOI: 10.1055/s-0036-1579759
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Li–Fraumeni Syndrome

Hernán Correa
1   Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
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Publication History

20 July 2015

10 August 2015

Publication Date:
13 April 2016 (online)

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Abstract

Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal dominant pattern of inheritance with high penetrance. These patients have a very high lifetime cumulative risk of developing multiple malignancies and have a strong family history of early-onset malignancies. The protein p53, encoded by TP53, has a complex set of genome-preserving functions initiated during episodes of cellular stress and DNA damage. In LFS, TP53 gene mutations cause the loss of function of p53, leading to downstream events permissive for development of various malignancies throughout life. The LFS component tumors include soft tissue sarcomas, osteosarcoma, premenopausal breast cancer, brain tumors, and adrenal cortical carcinomas. Multiple types of sarcomas have been reported in association with LFS; this review article will focus on the most frequently encountered pediatric sarcomas associated with TP53 mutations.

Keywords

Li–Fraumeni syndrome - TP53 - p53 - rhabdomyosarcoma - osteosarcoma
 

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