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

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.

References

  1. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D: Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992, 258: 818-821.

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  2. Stephanie S, Martine DF, Pascale CL: Compilation of published comparative genomic hybridization studies. Cancer Genet Cytogenet. 2002, 135: 63-90. 10.1016/S0165-4608(01)00624-0.

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Li, J., Zhang, X., Jensen, T. et al. Chromosomal imbalances mapped by array-based comparative genomic hybridization in an integrated approach to combat breast cancer in Denmark. Breast Cancer Res 7 (Suppl 2), P4.37 (2005). https://0-doi-org.brum.beds.ac.uk/10.1186/bcr1167

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  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/bcr1167

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