IDENTIFICATION OF AMPLIFIED DNA-SEQUENCES IN BREAST-CANCER AND THEIR ORGANIZATION WITHIN HOMOGENEOUSLY STAINING REGIONS

A modified comparative genomic hybridization (mCGH) technique was used to identify and map amplified DNA sequences in six homogeneously stai ning regions (hsr) from three primary breast carcinomas. Five differen t chromosomal regions and bands were identified as sites of amplificat ion: 8p1, 17q21.1, 17q23 (two cases), 19q13.3, and 20q13.3. The mCGH s ite located on 17q21.1 was demonstrated to correspond to a 50-100-fold amplification of ERBB2. Further in situ hybridization experiments wer e used to confirm the mCGH results and to characterize the organizatio n of the amplified sequences within the hsr. In five of six instances, two or more chromosomal regions were found amplified in the same hsr. In the tumor with the less modified karyotype, the two hsr comprised DNA sequences from three different chromosomes and showed different pa tterns of amplification. In the tumor with the most rearranged karyoty pe, the hsr-carrying chromosomes were formed by the translocation and amplification of sequences from three or four different chromosomal si tes. This illustrates the complexity of the amplification process in b reast cancers. (C) 1995 Wiley-Liss, Inc.