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Li-Fraumeni syndrome

D Gareth Evans, MD, FRCP
Section Editor
Patrick Y Wen, MD
Deputy Editor
Michael E Ross, MD


Li-Fraumeni syndrome is an inherited autosomal dominant disorder that is manifested by a wide range of malignancies that appear at an unusually early age [1,2]. Li-Fraumeni syndrome is also known as the Sarcoma, Breast, Leukemia, and Adrenal Gland (SBLA) cancer syndrome. This cancer predisposition syndrome is inherited as an autosomal dominant disorder and is associated with abnormalities in the tumor protein p53 gene (TP53).

The molecular pathogenesis of Li-Fraumeni syndrome, its clinical manifestations, diagnosis, and management, and implications for genetic counseling of patients and their families are reviewed here. The treatment of specific malignancies that develop in these patients is discussed separately.


The only gene that has been definitively associated with Li-Fraumeni syndrome is the tumor protein p53 gene (TP53), which is located on chromosome 17p13.1 [1-3]. Although mutations at two other locations (one at 1q23 and the checkpoint kinase 2 gene [CHEK2] locus at 22q12.1) have been postulated, there has been no validation of the 1q23 linkage, and CHEK2 has been discounted as a Li-Fraumeni gene [4]. TP53 is a tumor suppressor gene that has a major role in determining the fate of cells that contain damaged DNA. The gene product, tumor protein p53, can delay cell cycle progression, permitting an opportunity for DNA repair or initiation of programmed cell death (apoptosis). In the absence of the normal activated p53 protein, cells containing damaged DNA can survive and proliferate, which contributes to malignant transformation.

A variety of molecular techniques have been used to detect mutations in TP53, including sequence analysis of all or part of the gene, and techniques for detecting gene deletion or duplication. Over 300 distinct germline mutations of TP53 have been identified [5]. Missense mutations comprise the majority of these; most occur in exons 5 to 8, which are the DNA-binding region of the gene.

Li-Fraumeni syndrome is an autosomal dominant disease in which affected individuals have inherited one abnormal copy of TP53. In tumors from these patients, the second allele of TP53 is either somatically mutated or deleted, leaving cells with no functional gene product.


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Literature review current through: Aug 2017. | This topic last updated: Sep 05, 2017.
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