LETTER TO JMG

Low rate of TP53 germline mutations in breast cancer/sarcoma families not fulfilling classical criteria for Li-Fraumeni syndrome

D G R Evans¹, J M Birch², M Thorneycroft³, G McGown³, F Lalloo¹, J M Varley³

¹ Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Manchester M13 0JH, UK
² CRC Paediatric and Familial Cancer Research Group, Royal Manchester Hospital, Pendlebury, Manchester, UK
³ CRC Cancer Genetics Laboratory, Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 9BX, UK

Correspondence to:
Correspondence to:
Dr D G R Evans, Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK;
Gareth.Evans@cmmc.nhs.uk

Keywords: Li-Fraumeni syndrome; TP53; breast cancer; sarcoma

The first 150 words of the full text of this article appear below.

Breast cancer and sarcoma are key components of Li-Fraumeni syndrome (LFS).^1–6 Sarcoma, particularly childhood osteosarcoma or rhabdomyosarcoma in addition to childhood adrenocortical carcinoma (ACC), is the strongest predictor of the presence of a TP53 mutation.^7,8 However, while up to 80% of unselected series of ACC have TP53 germline mutations,⁸ only 3-10% of unselected sarcomas have been found to have such mutations.^9–11 At least half of these would have been predicted on the basis of family history and many of the rest could have arisen de novo.¹² While breast cancer is common in LFS and the penetrance of TP53 germline mutations in women for breast cancer may be as high as 56% by the age of 45 years (80% of female cancer incidence aged 16-45 years),^13,14 it is also common in the general population with nearly 2% of women now developing breast cancer by the age of 50 in the general . . . [Full text of this article]

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