Identifying and Characterizing Chromosomal Aberrations in Cancer Cells

Genomic instability is the hallmark of cancer. As cancer cells develop, they undergo dramatic DNA rearrangements such as chromosome loss or duplication and the translocation of DNA from one chromosome to another. The ability to decipher these changes helps researchers understand the onset and progression of cancer, develop targeted therapies, and create prognostic and diagnostic tools.

Comparative genomic hybridization (CGH) is a commonly used technique for studying the chromosomal copy number changes in cancer. Traditionally, it has been performed via optical imaging of whole chromosomes hybridized against differently labeled samples—an approach with limited sensitivity, resolution, quantification and throughput. Efforts to use microarrays to overcome these limitations have been—and continue to be—hampered by the inadequate sensitivity, resolution and flexibility of most microarray platforms.

A recent breakthrough by Agilent overcomes these scientific hurdles, enabling use of oligonucleotide microarrays to probe chromosomal changes in genomic DNA. This approach, called oligo array CGH (oligo aCGH), can identify precise areas of DNA loss and gain in cancer cells.

Accelerating the identification of key genes

Two products are driving this advance: the Agilent Human Genome CGH Microarray and the companion CGH Analytics software. Together, these form an oligonucleotide microarray-based solution that helps researchers explore chromosomal changes on the same technology platform they can use for gene expression analysis. This dual-purpose platform accelerates the identification of novel oncogenes and tumor suppressor genes, and enhances the overall understanding of the molecular pathways associated with oncogenesis.

The microarray provides complete genome-wide coverage with an emphasis on the most commonly studied genomic coding regions and cancer-related genes. Designed and validated specifically for oligo aCGH experiments, this microarray delivers three key benefits:

• Provides high resolution and high sensitivity measurements, enabling researchers to reliably identify single copy deletions, homozygous deletions and various sizes of amplicons.
• Requires only 25 nanograms of total genomic DNA to detect chromosomal changes across the entire genome.
• Simplifies experimental design and ease-of-use by handling complex genomic samples with full complexity.

The CGH Analytics software creates a visual environment for exploring oligo aCGH data and identifying specific genomic aberration patterns in that data. To enhance the analysis process, the software includes capabilities such as simultaneous visualization of multiple CGH microarray profiles, user-selectable calibration for comparison of profiles, and aberration summary reports (textual and graphical) that can be exported for publication and presentation. The software also supports data import and connections to third-party data analysis tools and displays.

To enhance overall oligo aCGH workflow, Agilent also provides DNA quality control capabilities via the Agilent 2100 bioanalyzer and DNA LabChip kits. The DNA LabChip kits can be used to check DNA digestion and labeling efficiency, and to infer the quality of array data.

For more information

To learn more about oligo aCGH and the Agilent microarray platform, you can view the e-Seminar "Interpreting the Consequences of Gene Gain and Loss" featuring Dr. Michael Bittner of the Translational Genomics Research Institute. For additional information about these and other Agilent life sciences products and resources, please visit the Life Sciences/Chemical Analysis main page.