ALLELIC LOSS AT CHROMOSOME 13Q12-Q13 IS ASSOCIATED WITH POOR-PROGNOSIS IN FAMILIAL AND SPORADIC BREAST-CANCER

Loss of heterozygosity (LOH) was analysed in 84 primary tumours from s poradic, familial and hereditary breast cancer using five microsatelli te markers spanning the chromosomal region I3q12-q13 which harbours th e BRCA2 breast cancer susceptibility gene, and using one other marker located within the RBI tumour-suppressor gene at 13q14. LOH at the BRC A2 region was found in 34% and at RBI in 27% of the tumours. Selective LOH at BRCA2 occurred in 7% of the tumours, whereas selective Loir at RBI was observed in another 7%. Moreover, a few tumours demonstrated a restricted deletion pattern, suggesting the presence of additional t umour-suppressor genes both proximal and distal of BRCA2. LOH at BRCA2 was significantly correlated to high S-phase values, low oestrogen an d progesterone receptor content and DNA non-diploidy. LOH at BRCA2 was also associated, albeit non-significantly, with large tumour size and the ductal and medullar histological types. No correlation was found with lymph node status, patient age or a family history of breast canc er. A highly significant and independent correlation existed between L OH at BRCA2 and early recurrence and death. LOH at RB1 was not associa ted with the above mentioned factors or prognosis. The present study d oes not provide conclusive evidence that BRCA2 is the sole target for deletions at 13q12-q13 in breast tumours. However, the results suggest that inactivation of one or several tumour-suppressor genes in the 13 q12-q13 region confer a strong tumour growth potential and poor progno sis in both familial and sporadic breast cancer.