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Agilent and TGen Announce Collaboration To Streamline CGH Oligo Arrays, Techniques

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Agilent Technologies this week announced a collaboration with the Translational Genomics Research Institute of Phoenix, Ariz., to test the technique of comparative-genomic hybridization on oligonucleotide-based microarray technology.

TGen will work with Agilent to benchmark and optimize Agilent's CGH microarrays and data analysis tools, Agilent said in a statement.

In collaborating with Agilent, TGen gains early access to Agilent Labs CGH microarrays and computational tools for analyzing and visualizing CGH data, and combined CGH and gene expression profile data.

Financial details of the collaboration were not disclosed.

The collaboration is notable in that it highlights microarray technology's ability to miniaturize and streamline existing assays, as well as Agilent's research and development program, which can uses the company's ink-jet based manufacturing system to develop custom oligonucleotide microarrays capable of providing answers comparable to results obtained with cDNA-based microarrays.

"We haven't done a detailed head-to-head comparison," said Laurakay Bruhn, project manager, Biomedical Assays Group, Molecular Diagnostics, Agilent Technologies. "What we have done is test whether 60-mer oligos made by Agilent's in situ synthesis would work for CGH. They do indeed work, and have sufficient sensitivity to show the types of chromosomal aberrations that people would like to see in CGH, like single-copy and two-copy deletions and amplifications as well. We have spent a considerable amount of effort working on developing probe-design rules for the pieces of DNA that are on the array, the oligos, to choose probes that work well for CGH."

Today, there are no commercial microarray products addressing this segment. Agilent's work in this area is still at the research and development stage, and has not yet been aimed toward a product launch date.

"The collaboration with TGen is to further develop the oligo CGH solutions," said Steve Laderman, manager of molecular diagnostics for Agilent Laboratories, the company's research and development arm. "As the performance has been validated through work of that sort, commercialization will follow. It is not easy to predict that precisely, but we are moving forward to see what might be possible."

Comparative genomic hybridization is a technique that has been in the peer-reviewed literature for more than a dozen years, and is considered a valuable tool in cancer research and one with promise for diagnosis.

Traditionally, the CGH assay is a molecular cytogenetic technique used for the analysis of the DNA content in malignant tumor cells. DNA from tumor tissue and from normal control tissue is labeled with different colored dyes. After mixing the tumor and reference DNA, the mix is hybridized to normal metaphase chromosomes or, for array- or matrix-CGH techniques, to a slide containing defined DNA probes. The (fluorescence) color ratio along the chromosomes is then used to evaluate regions of DNA gain or loss in the tumor sample. Gains can indicate an over-expression of oncogenes, while losses can indicate under-expression of tumor suppressor genes.

The result of the assay produces a map of DNA sequence copy number throughout the entire genome.

Today, cancer researchers have developed spotted cDNA microarrays to miniaturize this assay, taking advantage of the specificity offered by hybridizing DNA to the long probes of this particular array technology (see BAN 4/7/2004).

In May, at the 10th annual FDA Science Forum in Washington, Agilent presented a poster detailing its CGH research and development program, conducted in collaboration with scientists at the National Human Genome Research Institute and Agilent Laboratories to develop probe designs, and assay and data analysis methods for 60-mer oligonucleotide microarrays that are "compatible with CGH employing total genomic DNA."

"Our results demonstrate that in situ synthesized 60-mer oligonucleotide arrays can reproducibly detect genomic lesions including single copy and homozygous deletions, and variable amplicons throughout the genome," the poster summarized.

"The ability to closely analyze and view gene expression and high-resolution CGH data side by side could yield unprecedented insights into the nature of various cancers," Trent of TGen said in a statement. "In addition to shedding light on how tumors arise, these data could provide the foundation for diagnostic and prognostic tools, and help identify the most promising targets for drug development."

Agilent presented this work earlier in the year in Spain (see BAN 2/4/2004).

--MOK

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