BRCA2: a cause of Li–Fraumeni-like syndrome
- 1Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Manchester, UK
- 2CR-UK Paediatric and Familial Cancer Research Group, Royal Manchester Children’s Hospital, Manchester, UK
- Professor D G R Evans, University Department of Medical Genetics and Regional Genetic Service, St Mary’s Hospital, Hathersage Road, Manchester, M13 0JH, UK; gareth.evans{at}cmmc.nhs.uk
In response to a previous article outlining the search for other genes causing Li–Fraumeni syndrome (LFS),1 we have some evidence to suggest that BRCA2 may in some circumstances cause a Li–Fraumeni-like (LFL) pattern. Extensive analysis of classical LFS families has shown 70–75% with complete gene sequencing have identifiable mutations.1–3 A lower, but nevertheless substantial, proportion (30–40%) of families fulfilling criteria for LFL syndrome (box 1)2 also carry TP53 mutations. A recent paper has also suggested that BRCA2 may cause a fraction of breast sarcoma families.4 We have re-investigated an extensive LFL family (family 80) in whom we previously excluded TP53 by sequencing of all exons and by linkage5 and identified an exon 14–16 deletion in BRCA2.
Box 1
Li–Fraumeni syndrome (LFS) criteria
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Proband with any bone or soft tissue sarcoma, diagnosed under the age of 45 years
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one first degree relative with cancer under 45 years of age
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and one first or second degree relative in the same lineage, with cancer under 45 or sarcoma diagnosed at any age.
Li–Fraumeni-like syndrome (LFL) criteria
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Proband with any childhood cancer or sarcoma, …
