last update: 22/05/2006

Background to disease

Li-Fraumeni syndrome (LFS) is a rare familial cancer syndrome of diverse tumours. Gene carriers have a 90% risk of developing cancer by age 50. The spectrum of cancers seen in this syndrome include soft tissue sarcomas, brain tumours, osteosarcomas, adrenocortical carcinomas, breast cancer and leukaemia These often develop at an early age.

Strict diagnostic criteria apply to the definition of a Li-Fraumeni family, requiring that the index case is diagnosed with sarcoma before 45 years of age and there are two first degree relatives with sarcoma or another characteristic tumour before 45 years. Families that show features of LFS but do not fit these stringent criteria are termed Li-Fraumeni like (LFL) families.

Over half of all families conforming to the definition of classic LFS and approximately one quarter of those which are LFL carry germline mutations in the p53 gene. 85% of mutations seen in LFS are missense The transition of 5-methycytosine to thymine at CpGs in p53 is proposed to contribute significantly to the mutation spectrum. Mutations are clustered in the three loops that form the DNA binding domain, with 84% of mutations detected in exons 5,7 and 8.

Linkage studies are useful in the exclusion of the involvement of p53 in LFS families. The p53 coding region is highly conserved, however arginine -proline polymorphism does exist in exon 4. Two intragenic polymorphic repeats have also been identified, a pentanucleotide repeat in intron 1 and a dinucleotide repeat p53CA.

OMIM # 151623

Gene OMIM # 191170

Laboratory analysis

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User Guide Editor: Dr Ruth Charlton PhD DipRCPath. Copyright © 2007 . Yorkshire Regional DNA Laboratory. All rights reserved.