Li–Fraumeni Syndrome

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Li–Fraumeni Syndrome

Carol Portwine, The Hospital for Sick Children, Toronto, Ontario, Canada
David Malkin, The Hospital for Sick Children, Toronto, Ontario, Canada

Published online: April 2001

DOI: 10.1038/npg.els.0001893

Full Article on Wiley Online Library

Abstract
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References

The Li–Fraumeni syndrome is a rare inherited predisposition to the development of multiple cancer phenotypes at an early age which is attributed primarily to germline mutations of the p53 tumour suppressor gene. Identification of these families is important in the study of cancer and the development of ethical and appropriate screening modalities, prevention, early cancer detection, and treatment of individuals who harbour alterations of such cancer genes, in order that we may one day improve their prognosis.

Keywords: tumour suppressor gene; p53; li–fraumeni syndrome; cell cycle; predictive screening

References
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Further Reading
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	Li FP and Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Annals of Internal Medicine 71: 747–752.
	Tainsky MA, Bischoff FZ and Strong LC (1995) Genomic instability due to germline p53 mutations drives preneoplastic progression toward cancer in human cells. Cancer Metastasis Reviews 14: 43–48.
	Varley JM, Evans DG and Birch JM (1997) Li–Fraumeni syndrome – a molecular and clinical review. British Journal of Cancer 76: 1–14.
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Article Title:	Li–Fraumeni Syndrome
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	Figure 1. Classical Li–Fraumeni pedigree. Squares represent males and circles represent females. Shaded symbols represent affected individuals. Crossed individuals are deceased. Numbers indicate age at diagnosis.
	Figure 2. p-53 consists of 393 amino acids with four structural and five evolutionarily conserved domains (purple boxes). The four structural domains are the transactivation domain (codons 1–42; red), the central DNA-binding domain (codons 102–292; orange), the tetramerization domain (codons 324–355; blue) and the regulatory domain (codons 367–393; green). Note the mutational hotspots (pink bars) within the conserved domains. Examples of protein and viral binding sites are indicated, which can also lead to inhibition of p-53 function.
	Figure 3. p-53 at the G1–S phase of the cell cycle. DNA damage leads to p-53 accumulation, resulting in cell cycle arrest to allow for DNA repair. If the damage is too great for repair, then p-53 can lead to apoptosis to prevent propagation of genetic changes. E2F represents a family of transcription factors. Cdk, cyclin-dependent kinase; P, phosphate group; pRb, Retinoblastoma protein.

Li–Fraumeni Syndrome

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