title: 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.
authors.affiliation: UCSF Cancer Center, University of California San Francisco, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nishizaki
authors.forename: S
authors.initials: S
authors.lastname: DeVries
authors.forename: K
authors.initials: K
authors.lastname: Chew
authors.forename: W H
authors.initials: WH
authors.lastname: Goodson
authors.forename: B M
authors.initials: BM
authors.lastname: Ljung
authors.forename: A
authors.initials: A
authors.lastname: Thor
authors.forename: F M
authors.initials: FM
authors.lastname: Waldman
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008677:Metaphase; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D016650:Fluorescein-5-isothiocyanate