The Icelandic founder mutation BRCA2 999del5: analysis of expression

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The Icelandic founder mutation BRCA2 999del5: analysis of expression

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R284 Introduction Mutations in BRCA1 and BRCA2 are associated with a high risk of developing cancer of the breast, of the ovaries and of other organs [1]. A large number of cancer- associated mutations in these genes have been described to date; however, few studies have directly probed the functional consequences of individual mutations [2–5]. One question that has thus rarely been addressed is whether the increased risk of cancer is simply due to the lack of one healthy copy of the gene (haploinsufficiency) or whether the gene produces a protein product that interferes with normal cellular processes. Most nonsense (insertion/deletion) mutants are thought to result in unstable transcripts and in little or no mutant protein production [6]. Exceptions to this rule are found, however, also among the BRCA genes where proteins encoded by the following mutant genes have been detected: BRCA1 5382insC (Breast Cancer Consortium) and BRCA2 6174delT [2]. Perhaps the most intriguing evidence for a potential functional role for truncated BRCA2 mutants comes from the observation that cancer risk is affected by the location of the mutation. Mutations in a central portion of BRCA2, commonly termed the ovarian cancer cluster region, are thus associated with bp = base pairs; DMEM = Dulbecco’s modified Eagle’s medium; ELISA = enzyme-linked immunosorbent assay; FCS = fetal calf serum; wt = wild type. Breast Cancer Research Vol 6 No 4 Mikaelsdottir et al. Research article The Icelandic founder mutation BRCA2 999del5: analysis of expression Evgenia K Mikaelsdottir1,2, Sigridur Valgeirsdottir3, Jorunn E Eyfjord1,2 and Thorunn Rafnar3 1Molecular and Cell Biology Laboratory, The Icelandic Cancer Society, Reykjavik, Iceland 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland 3Iceland Genomics Corporation, Reykjavik, Iceland Corresponding author: Thorunn Rafnar (e-mail: [email protected]) Received: 24 Nov 2003 Revisions requested: 3 Feb 2004 Revisions received: 6 Feb 2004 Accepted: 10 M


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