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Editor—BRCA1 is one of the major breast and ovarian cancer susceptibility genes. Many studies have suggested that the BRCA1 protein is multifunctional. Notably, it may play a role in DNA repair, especially in double strand break (DSB) DNA repair by homologous recombination because (1)BRCA1 acts in association with Rad51,1 2 (2) DNA damage induces its phosphorylation and delocalisation from nuclear foci to the DNA replication forks,3 and (3) it contains a zinc finger domain that interacts with BARD1, an effector of DNA repair,4 and two BRCT (BRCA1 C-terminal) domains which are found in various proteins implicated in DNA repair5 6(fig 1A).
Among the various genetic alterations found in breast tumours, one is called microsatellite instability (MI). MI has been shown in a small fraction of sporadic breast tumours, varying from 0 to 30%,7 and in familial breast tumours conflicting results have been reported with a MI+ tumour frequency of 0% (0/15) according to Lothe et al 8 and 83% (15/18) according to Glebov et al. 9
MI is characterised by expansion …