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Since its invention by Kallioniemi and colleagues in 1992 [1], comparative genomic hybridization (CGH) has revolutionized the detection and mapping of chromosomal imbalances in neoplasias. However, conventional CGH is handicapped by its low resolution. Array-based CGH brings the resolution towards a molecular level. With a capillary printer we produce arrays on CodeLink slides with 3158 BAC clones, which randomly represent the whole genome. With our homemade arrays, we can detect and map numerical aberrations in a single experiment with about 1 Mb resolution. Furthermore, we have optimized printing, labeling, hybridization, scanning and analysis tools. Reverse-labeling (exchanging the tumor and reference DNA labeling dyes) gives us reliable results even in samples with a substantial admixture of normal cells.  In the Danish Centre for Translational Breast Cancer Research, a 5-year project involving 500 high-risk patients is underway. Both prospective and retrospective studies are planned with a systems biological approach involving a multitude of analyses, including array-CGH. Twenty breast cancer samples have been analyzed in a preliminary study. Chromosome 1q (15/20), chromosome 8 (14/20), chromosome 11 (5/20), chromosome 17q (9/20) and chromosome 20q (6/20) gains (duplications and amplifications), and chromosome 22 (7/20) deletions are the most frequent aberrations, which is consistent with the previously published conventional CGH results [2]. Our findings will continuously be integrated with all the other results from the same tumors.

Chromosomal imbalances mapped by array-based comparative genomic hybridization in an integrated approach to combat breast cancer in Denmark