PATTERNS OF ALLELE LOSSES SUGGEST THE EXISTENCE OF 5 DISTINCT REGIONSOF LOH ON CHROMOSOME-17 IN BREAST-CANCER

Chromosome 17 is a frequent target during breast-cancer formation and progression. It has been shown to be affected by allele losses at mult iple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of br east tumors. To this end we analyzed 151 pairs of tumor and cognate ly mphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by P CR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thra I, gcsf and rara genes. Data pr esented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17: 2 on 17p, 3 on 17q. Of the 2 regions o n 17p, one involves tp53 while the second is located more distally tow ard the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long a rm band q21, corresponding to the brcaI region; (ii) in a central regi on defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regi ons presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large por tions of the chromosome, a high proportion of the analyzed tumors show ed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2. An altered chromosome 17 (bearing an LOH or a DNA amplification) was found in more than 80% of the breast t umor set analyzed here and multiple anomalies affecting this chromosom e were often detected in the same sample. (C) 1994 Wiley-Liss, Inc.