MICROSATELLITE INSTABILITY IN EARLY SPORADIC BREAST-CANCER

We have studied the incidence of microsatellite instability at three t rinucleotide repeats and seven dinucleotide repeats from five chromoso mal regions, in a group of 30 mammographically detected 'early' invasi ve breast cancers and correlated its occurrence with clinicopathologic al parameters. The myotonic dystrophy(-)(DM-1) trinucleotide repeat wa s analysed in 48 additional cases. In 4 out of 78 (5%) paired tumour-n ormal DNA samples we found evidence of somatic microsatellite instabil ity at DM-1: a novel allele of a different size was seen in the tumour DNA which was not present in the normal DNA sample, All four tumours that showed evidence of instability were from the core group of 30 cas es (13%) and were well or moderately differentiated, oestrogen recepto r-positive, infiltrating ductal carcinomas. Two of these tumours were unstable at nine of ten loci studied, both trinucleotide and dinucleot ide repeals. DNA prepared from different normal tissues showed no evid ence of instability, for all four instability cases. These data indica te that microsatellite instability is specific to the tumour DNA and i s an early event in the genesis of some sporadic breast cancers.