Genetic alterations in primary breast cancers and their metastases: Direct comparison using modified comparative genomic hybridization

Abstract

Breast tumor development and progression are thought to be driven by an accumulation of genetic alterations, but little is known about the specific changes that occur during the metastatic process. We analyzed pairs of primary breast cancers and their matched lymph node metastases from 11 patients, pairs of primaries and distant metastases from three patients, and pairs of primaries, and local recurrences from two patients by using comparative genomic hybridization (CGH). Simultaneous hybridization analysis of primary versus matched lesion DNAs from 11 patients was also performed (modified CGH). This modified approach was useful not only for confirming CGH results but also for demonstrating quantitative differences between aberrations present at both sites. Frequent chromosomal changes present at both sites (>35% of 16 cases) were 1q, 8q, and 17q gains and 6q, 8p, 9q, 13q, 16q, 17p, and Xp losses. The total number of aberrations detected exclusively in the lymph nodes 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 metastases (two lymph nodes and two distant metastases), but none in any primary tumor. These findings suggest that progression from primary breast cancer to metastasis may be associated with the acquisition of further 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. Genes Chromosom. Cancer 19:267–272, 1997. © 1997 Wiley‐Liss, Inc.

Comparative Genomic Hybridization of Microdissected Familial Ovarian Carcinoma: Two Deleted Regions on Chromosome 15q Not Previously Identified in Sporadic Ovarian Carcinoma

“…A final region of interest is 9q31-33 that showed loss in 16 of 36 (44%) familial ovarian cancer cases. Loss of 9q has been seen in unselected ovarian cancer (Table 2) and harbors a region that is commonly associated with bladder and renal cell carcinoma (Habuchi et al, 1997;Simoneau et al, 1996), although loss of heterozygosity (LOH) of this region has also been linked to metastatic breast cancer (Minobe et al, 1998;Nishizaki et al, 1997). Our analyses suggest that losses at 17p12-13, Xp22, 18q21, 13q14, and 9q31-33 in ovarian cancer are unrelated to hereditary predisposition.…”

Comparative Genomic Hybridization Analysis of Myoepithelial Carcinoma of the Breast

“…None of the alterations identified in myoepithelial carcinomas are unique, and they have been previously described in invasive breast carcinomas with luminal phenotype (Buerger et al, 1999;Nishizaki et al, 1997;Roylance et al, 1999;Schwendel et al, 1998;Tirkkonen et al, 1998). The most common alterations identified in myoepithelial carcinoma (loss of 16q and 17p) are also regions commonly deleted in ductal carcinomas of no special type.…”

“…The most striking observation from this study is the paucity of alterations identified in myoepithelial carcinomas (mean 2.1) compared with "ordinary" breast carcinomas having luminal differentiation. The mean number of alterations reported in the literature in Grade I invasive ductal carcinomas of no special type is 5.4 (range of means is 3.6 -8.0), and 11.7 in Grade III tumors (range of means 8.4 -13.8) (Buerger et al, 1999;Nishizaki et al, 1997;Roylance et al, 1999;Schwendel et al, 1998;Tirkkonen et al, 1998). The data in myoepithelial tumors are surprising in view of their aggressive morphology and behavior.…”

Amplification of c-myc by Fluorescence In Situ Hybridization in a Population-Based Breast Cancer Tissue Array

“…The copy number alterations of chromosome 8 detected by comparative genomic hybridization typically consist of gains on the q-arm, either entire 8q or only its telomeric parts (3)(4)(5). These aberrations have commonly been interpreted to reflect amplification of the c-myc oncogene, which is located at 8q24.1.…”