Low frequency of microsatellite instability in BRCA1 mutated breast tumours

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Abstract
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). Figure 1 (A) Schematic representation of the wild type BRCA1 protein with the regions involved in DNA repair shown in black: (a) zinc finger domain (AA 20-68), (b) interaction with Rad51 (AA 758-1064), (c1 and c2) BRCT motifs (respectively AA 1699-1736 and AA 1818-1855). (B) Schematic representation of the BRCA1 mutated proteins generated by germline mutations in the 10 French breast/ovarian cancer families studied. *A Hardouin, personal communication, †C Maugard, personal communication. 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 …

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