GENETIC ALTERATIONS ON CHROMOSOME-17 IN HUMAN BREAST-CANCER - RELATIONSHIPS TO CLINICAL-FEATURES AND DNA-PLOIDY

We analyzed DNA from 105 primary breast cancers to assess amplification of the ERBB2 gene and loss of heterozygosity (LOH) on chromosome 17 using 4 polymorphic markers, and investigated the relationships of these genetic alterations to clinicopathological characteristics including DNA ploidy. Amplification of the ERBB2 gene was observed in 28% of the tumors. ERBB2 was amplified in tumors of all clinical stages and amplification was significantly linked to lymph node metastasis. LOH at D17S5 was observed in 28 of 57 informative tumors, while 17 of 62 informative tumors showed allelic loss at TP53. Among the 37 tumors informative for both loci, 32% showed LOH at these loci and 49% retained both alleles, indicating that there was a significant relationship between LOH at D17S5 and at TP53. We also examined LOH at the D17S74 and NME1 loci on chromosome 17q. LOH at D17S74 and NME1 was observed in 20% and 22% of the informative tumors, respectively, but there was no significant association between LOH at these loci. Of the 4 loci tested, LOH at TP53, D17S74, and NME1 was associated with clinical stage. Lymph node metastasis was correlated with LOH at NME1. Moreover, allelic loss was more frequent in aneuploid tumors than in diploid tumors. These results suggest that certain combinations of genetic alterations on chromosome 17 may cooperate in the development and/or progression of breast cancer. Furthermore, it seems likely that analysis of these alterations in breast cancer patients may provide useful prognostic information.