GENETIC AND MOLECULAR HETEROGENEITY OF BREAST-CANCER CELLS

We have undertaken a systematic study of primary human breast tumor DN As to identify and characterize frequently occurring somatic mutations . Loss of heterozygosity (LOH) was found on chromosomes 1p (37%), 1q ( 20%), 3p (30%), 7 (41%), 13q (30%), 17p (49%), 17q (29%) and 18q (34%) in our tumor DNA panel. Specific subsets of tumors could be defined b ased on the particular collection of mutations they contained. One goa l of these studies has been to determine whether there is a significan t association between specific mutations and clinical parameters of th e disease. We have found that LOH on chromosome 17p in tumor DNAs is a ssociated with breast tumors having a high proliferative index and tha t LOH on chromosome 7 is associated with patients having a poor progno sis. Our analysis of chromosome 17 suggests that there may be as many as four tumor suppressor genes affected in primary human breast tumors .