Evaluation of RAD50 in familial breast cancer predisposition

Johanna Tommiska, Sheila Seal, Anthony Renwick, Rita Barfoot, Linda Baskcomb, Hiran Jayatilake, Jirina Bartkova, Jonna Tallila, Milja Kaare, Anitta Tamminen, Päivi Heikkilä, D. Gareth Evans, Diana Eccles, Kristiina Aittomäki, Carl Blomqvist, Jiri Bartek, Michael R. Stratton, Heli Nevanlinna*, Nazneen Rahman, A. Ardern-JonesR. Belk, J. Berg, N. Bradshaw, G. Brice, A. Brady, C. Brewer, B. Bullman, R. Cetnarsryj, C. Chapman, T. Cole, G. Crawford, C. Cummings, R. Davidson, A. Donaldson, H. Dorkins, R. Eeles, F. Emslie, G. Evans, S. Goff, J. Gray, L. Greenhalgh, H. Gregory, N. Haites, S. Hodgson, T. Homfray, R. Houlston, L. Izatt, L. Jackson, L. Jeffers, F. Lalloo, M. Longmuir, D. McBride, J. Mackay, A. Magee, S. Mansour, P. Morrison, V. Murday, J. Paterson, M. Porteous, N. Rahman, M. Rogers, S. Rowe, A. Schofield, J. Shea-Simmonds, L. Side, L. Snadden

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


The genes predisposing to familial breast cancer are largely unknown, but 5 of the 6 known genes are involved in DNA damage repair. RAD50 is part of a highly conserved complex important in recognising, signalling and repairing DNA double-strand breaks. Recently, a truncating mutation in the RAD50 gene, 687delT, was identified in 2 Finnish breast cancer families. To evaluate the contribution of RAD50 to familial breast cancer, we screened the whole coding region for mutations in 435 UK and 46 Finnish familial breast cancer cases. We identified one truncating mutation, Q350X, in one UK family. We screened a further 544 Finnish famlial breast cancer cases and 560 controls for the 687delT mutation, which was present in 3 cases (0.5%) and 1 control (0.2%). Neither Q350X nor 687delT segregated with cancer in the families in which they were identified. Functional analyses suggested that RAD50 687delT is a null allele as there was no detectable expression of the mutant protein. However, the wild-type allele was retained and expressed in breast tumors from mutation carriers. The abundance of the full-length RAD50 protein was reduced in carrier lymphoblastoid cells, suggesting a possible haploinsufficiency mechanism. These data indicate that RAD50 mutations are rare in familial breast cancer and either carry no, or a very small, increased risk of cancer. Altogether, these results suggest RAD50 can only be making a very minor contribution to familial breast cancer predisposition in UK and Finland.

Original languageEnglish
Pages (from-to)2911-2916
Number of pages6
JournalInternational Journal of Cancer
Issue number11
Publication statusPublished - 1 Jun 2006


  • Breast cancer
  • Cancer susceptibility
  • Familial
  • RAD50


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