MICROSATELLITE INSTABILITY AND LOSS OF HETEROZYGOSITY IN PRIMARY BREAST-TUMORS

Allelic imbalance or loss of heterozygosity (LOH) studies have been us ed extensively to identify regions on chromosomes that may contain put ative tumour suppressor genes. We looked for evidence of microsatellit e instability (MI) and LOH on chromosome 7q, 10q, lip and 17q using se ven polymorphic microsatellite markers, In 42 paired breast cancer-per ipheral blood DNA samples we identified 24 tumours (57%) exhibiting ge netic alterations, Twenty-one specimens exhibited LOH (50%), while 11 specimens exhibited MI (26%) in at least one microsatellite marker. Th e most frequent incidence of LOH was found for the marker THRA1 (8/33, 24%) indicating that thra1 gene becomes a strong candidate tumour sup pressor gene, whereas of MI it was D10S109 (3/26, 12%). These MI and L OH data were analysed using a range of clinicopathological parameters, Tumours displaying MI with no evidence of LOH and tumours exhibiting MI and LOH belonging to stage II or III were found, however none were at stage I. These data suggest that MI may be an early event in mammar y tumorigenesis whereas LOH occurs at a late stage, A significant asso ciation between the absence of oestrogen receptors (p < 0.01) and the absence of both oestrogen and progesterone receptors (p < 0.001) at 17 q21 were observed, indicating a possible relationship between specific genetic changes at this region and hormonal deregulation in the progr ession of breast cancer.