GENETIC ALTERATIONS IN PRIMARY BREAST CANCERS AND THEIR METASTASES - DIRECT COMPARISON USING MODIFIED COMPARATIVE GENOMIC HYBRIDIZATION

Breast tumor development and progression are thought to be driven by a n accumulation of genetic alterations, but little is known about the s pecific changes that occur during the metastatic process. We analyzed pairs of primary breast cancers and their matched lymph node metastase s from 11 patients, pairs of primaries and distant metastases from thr ee patients, and pairs of primaries, and local recurrences from two pa tients by using comparative genomic hybridization (CGH). Simultaneous hybridization analysis of primary versus matched lesion DNAs from 11 p atients was also performed (modified CGH). This modified approach was useful not only for confirming CCH results but also for demonstrating quantitative differences between aberrations present at both sites. Fr equent chromosomal changes present at both sites (>35% of 16 cases) we re 1q, 8q, and 17q gains and 6q, 8p, 9q, 13q, 16bq, 17p, and Xp losses . The total number of aberrations detected exclusively in the lymph no des or distant metastases was higher than that in the primary tumors ( 2.5 vs. 0.7, P < 0.05). We found high-level amplifications in four met astases (two lymph nodes and two distant metastases), but none in any primary tumor. These findings suggest. that progression from primary b reast cancer to metastasis may be associated with the acquisition of f urther genetic changes. Although further investigations are required, it was of interest that 3 of 11 patients (27%) showed 18q loss solely in their lymph node metastases. (C) 1997 Wiley-Liss, Inc.