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BlueGnome Debuts Cancer Cytogenomics Microarray Consortium-Designed Arrays

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By Justin Petrone

BlueGnome this week announced the first shipments of CytoChip CCMC, a new microarray-based kit for researchers that includes arrays designed by the Cancer Cytogenomics Microarray Consortium along with the company's database and analysis software.

Officials from BlueGnome and the CCMC said that they hope the wider availability of the arrays will spur cancer cytogenetics researchers to adopt the consortium's design, and further the efforts of the CCMC to set standards for the use of arrays in cytogenetics.

BlueGnome officials also said that they believe the availability of the array design will enable them to create new products for cancer researchers.

"We now supply laboratories in over 30 countries, many of whom routinely perform [fluorescent in situ hybridization] and other classical cytogenetic techniques on bone marrow and other cancer samples," Graham Snudden, vice president of engineering at Cambridge-based BlueGnome, told BioArray News this week. "We see the CCMC as a critical first step in the wider adoption of arrays" in cancer cytogenetics.

Marilyn Li, a member of the CCMC's steering committee and director of the Cancer Genetics Laboratory at Baylor College of Medicine in Houston, said that the organization will have to wait and see if the wider availability of the consortium-designed chips will increase adoption of the design, but added personally she is inclined to think it will.

"I truly believe that the design is good," Li told BioArray News this week. "One of its great advantages is that it is cancer-specific. The more people who use it, the earlier we can establish a cancer microarray database to which physicians as well as researchers can refer."

The CCMC was formed last year by a group of clinical cytogeneticists, molecular pathologists, and molecular geneticists who are interested in applying microarray-based comparative genomic hybridization and genotyping technologies to cancer diagnosis and cancer research. Among the consortium's aims are to set platform-neutral standards for cancer microarray designs and to create cancer-specific platforms suitable for diagnosis, to create a public cancer array database, and to carry out multicenter cancer genome research (BAN 11/30/2010).

One organization that has inspired the CCMC is the International Standard Cytogenomic Arrays consortium, which has created a standard array design used to detect constitutional abnormalities. These are sold by a number of firms, including BlueGnome.

The availability of a standard design for constitutional genetics, as well as a shared database that can be used to make calls, are some of the factors that led the American College of Medical Genetics to revise its guidelines in September to make microarrays a first-line test in the diagnosis of genetic abnormalities (BAN 9/28/2010).

Some members of the CCMC believe that once it is able to set standards for using arrays in cancer cytogenetics, professional organizations like the ACMG will revise their own guidelines to include the use of microarrays. For instance, this was done in the case of constitutional testing following the efforts of the ISCA.

That could in turn cause more researchers to adopt arrays for cancer research, as adoption in the oncology community has lagged constitutional geneticists', in part due to the difficulty of interpreting results. CCMC steering committee member Jill Hagenkord told BioArray News last month that "once the standard guidelines come out, [adoption] is going to go very quickly."

Hagenkord is medical director of the Molecular Pathology and Clinical Genomics Laboratories at Creighton Medical Laboratories in Omaha, Neb., and the founder and chief medical officer of startup iKaryos Diagnostics (BAN 11/30/2010).

Getting the CCMC-designed arrays into more labs so that they can generate data that is later entered into a common database is a goal of the consortium. Still, while the CCMC boasts 240 participating companies and organizations, many of whom are also ISCA members, only about 15 labs currently use its standard design for cancer research, according to Li. She said she hopes that number will rise with BlueGnome's offering.

CCMC's website said it chose more than 130 cancer-associated genomic regions to build the chip, which currently contains 500 cancer genes. The genes are separated into two groups: well-defined cancer genes commonly involved in different cancers, and those that are relatively new members of the cancer-gene family.

Agilent Technologies manufactures the arrays, which include about 20,000 cancer-associated probes, while the remaining probes are relatively evenly distributed throughout the genome, representing its backbone. The CCMC has also made the design available to other large array manufacturers, including Affymetrix, Illumina, and Roche NimbleGen.

Li stressed that the CCMC is a platform-agnostic organization.

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She also has acknowledged that the CCMC has discussed with BlueGnome rival Oxford Gene Technology the possibility that the company could sell the Agilent-manufactured design with its own software. Like BlueGnome, Oxford-based OGT sells ISCA-designed chips.

"The CCMC has no contract with BlueGnome," Li said this week. BlueGnome does not make the arrays, she noted. Rather, the shop makes software that is used to analyze array data; it buys arrays from Agilent and sells them along with its software.

According to Li, all users of the CCMC design must agreement to not copy, revise, or resell the CCMC design to any third party without the consent of the CCMC. They must also agree that they will contribute to the CCMC database, she added.

James Clough, vice president of clinical and genomic services at OGT, told BioArray News this week that the firm is "currently evaluating a range of designs including the CCMC [design]" while it decides in which areas of cancer aCGH arrays will play the greatest role.

These different designs are "being evaluated in a research setting by customers around the world" and the firm is "making sure that all cancer arrays are extensively tested in the research setting before offering them for wide market availability." OGT anticipates that a number of designs will be rolled out during 2011, Clough said.

The View from Cambridge

BlueGnome's new cancer platform combines the CCMC array design with the company's BlueFuse database and analysis software. Snudden said that the main benefit of using BlueFuse is that it "stores all results in a single SQL database together with all the experimental conditions." The database enables the firm's customers to select and visualize all the results relating to certain cancers.

"These results can then be summarized in a track in the software and used in the interpretation and classification of future samples," Snudden said. "This ability to share results in this way is one of the CCMC's central aims, which is why the software is so important."

The new arrays also complement BlueGnome's menu of arrays for cancer research, Snudden noted. Two years ago, BlueGnome launched its CytoChip Focus Hematology, which screens for more than 50 genomic regions associated with known hematological malignancies (BAN 9/2/2008).

"We believe the CytoChip CCMC will complement the CytoChip Focus Hematology," Snudden said. "The CytoChip CCMC has a much higher probe density while the CytoChip Focus Hematology is designed to report only those imbalances with a known interpretation.

"Both arrays use the same BlueFuse software so the customer is able to select the array which best suits their requirements in terms of resolution but also speed of the protocol and amount and quality of starting material," he added.

Snudden said cancer researchers currently use a variety of BlueGnome products in their projects. He said that some have used the CytoChip Focus Hematology to investigate bone marrow while others have used its CytoChip Oligo arrays — both the ISCA design and BlueGnome's own constitutional design.

"The CCMC design enables us to offer a common cancer design on the CytoChip Oligo platform and therefore represents a significant step forward," he said. The company also believes the launch of the CCMC-designed arrays could lead to new products. BlueGnome CEO Nick Haan said in a statement this week that the launch of the CCMC array is the "start of a very exciting development."

He said the firm is already applying its "expertise in advanced mathematics and data visualization to deliver a suite of new algorithms which will enable researchers to identify the relevant information hidden in the massive amount of raw data that is delivered by the CCMC microarrays."

While he acknowledged that the analysis of cancer microarray data is "very challenging," Snudden said the company feels "we are in a good position to take this on as we have all our samples in a single database and also have a strong research background in biomarker discovery and associated numerical methods."

He said that BlueGnome is already looking at more advanced region-detection algorithms, but that it will need to understand how these perform on a wide range of results.

"We will therefore be working with all our CCMC customers in order to better understand how they wish to interpret these samples and what algorithms will be required to help them do this efficiently and reproducibly," he said.


Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.

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