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Geneticists Ally with Vendors to Foster Growing Cancer Cyto Community

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While adoption of arrays for clinical testing is still in its early stages, some members of the Cancer Cytogenomics Microarray Consortium at their annual meeting in Chicago last week praised an ongoing dialogue between the CCMC and array vendors, and stated that they hope that the availability of new cancer-focused arrays and data analysis tools will spur the uptake of the technology and ultimately lead to better treatment decisions for patients.

Likewise, vendors are counting on the CCMC to develop guidelines, carry out quality control studies, and establish the community infrastructure to see arrays become a standard tool in clinical cancer cytogenetics, following a path similar to the International Standards for Cytogenomic Arrays consortium, which laid the foundation for the acceptance of chromosomal microarrays as the first-tier technology for postnatal pediatric testing (BAN 9/28/2010).

CCMC President Anwar Iqbal told BioArray News during the meeting that the CCMC has signed agreements with two vendors, Agilent Technologies and Oxford Gene Technology, to allow the firms to use the CCMC gene list to design their products, and the CCMC name to market them.

He added that the CCMC, a nonprofit, has been in discussions with Affymetrix, BlueGnome, and Illumina concerning array design, but has not signed any agreements with them (see related story, this issue).

Still, Iqbal noted that all of the array vendors have been supportive of the community, as Affy, Agilent, BlueGnome, Illumina, and OGT were among the meeting's sponsors, in addition to BioDiscovery, CytoCell, PerkinElmer, and Tecan.

Marilyn Li, director of the Cancer Genetics Laboratory at Baylor College of Medicine and CCMC member, said that one of the CCMC's duties is to work with vendors to "design and validate arrays that can help the community." Information on CCMC's recommended gene list is publicly available, Li told BioArray News at the meeting, but if vendors want to use the CCMC name, they have to reach an agreement with the consortium.

"All the vendors have been very supportive to get things going," said Robert Best, director of the division of genetics at the University of South Carolina School of Medicine.

"CCMC was designed as an ecumenical environment," Best said. "We didn't want to favor one company over another. The [vendors] have all come to the table to support us."

As for what is on the market, Best said that "all the available platforms work well," and cited the CCMC's recently completed quality control study as evidence that "across platforms, on different days in the same labs and across labs, it all works out" (BAN 12/6/2011).

At the same time, Best said that the community needs more data analysis tools. "To make the calls we are making now, I think the available software is working well, and we saw that different labs with different platforms made the same calls in the QC study," said Best.

Different Choices

So far, Agilent is the only array vendor to bring chips to market that are based on the CCMC's designs. Last fall, the company launched its SurePrint G3 Human CGH+SNP Cancer Microarrays, and the firm has seen "a lot of interest" from the cancer cytogenomics community since launching the product, Heidi Kijenski, director of clinical marketing at Agilent, told BioArray News this week.

Kijenski noted that Agilent customers are particularly interested in custom arrays, and said that most cancer microarray customers design their own chips using the CCMC content and add probes that are of interest to them, such as lung cancer genes or prostate cancer genes.

"Agilent can include any content on our arrays and we have customers who design their own cancer arrays with the CGH+SNP probes that cover their cancer genes of interest," said Kijenski.

Oxford, UK-based OGT will most likely be the next firm to debut an array based on the CCMC's design. Stephen Archibald, the firm's marketing communications manager, confirmed with BioArray News this week that OGT has signed an agreement with the CCMC.

OGT just recently launched an oncology-focused comparative genomic hybridization-plus-SNP chip designed in collaboration with the University of Lausanne's Jacqueline Schoumans that contains content relevant to hematological malignancies and solid tumors. The company also sells another chip that is focused soley on hematological cancers.

Archibald said that OGT decided to add the new CCMC-designed array menu because it is "important to offer customers a choice" and because "some researchers may prefer the standard design developed by the CCMC, which contains well validated content and is currently being adopted in a number of labs."

Like Agilent, OGT has seen "significant interest" in its cancer-focused arrays, and said that "many researchers" are using microarrays to replace or add to standard [fluorescence in situ hybridization] panels.

While Agilent and OGT have elected to sign agreements with the CCMC, other vendors so far have not.

Sally Cartwright, marketing manager at Cambridge, UK-based BlueGnome, confirmed with BioArray News this week that no deal has been inked with the CCMC. However, she noted that the firm's CytoChip Cancer design includes 670 cancer genes, "many of which will be in common" with the CCMC's design.

According to Cartwright, BlueGnome completed validation of the CytoChip Cancer design in collaboration with the BlueGnome Cancer Workgroup, a consortium of 12 North American microarray laboratories.

Affy also has not signed an agreement to use the CCMC's design or name. Richard Shippy, Affy's director of strategic product marketing for clinical applications, told BioArray News that the company's 2.6-million-marker CytoScan HD offering "covers every gene in the genome," including the CCMC's list.

"Other microarray providers make choices about which genes to cover densely," said Shippy. "This is due to marketing philosophy as well as manufacturing limitations constraining printing density," he said. "We have instead taken the approach to cover all genes with increased coverage in cancer-related and constitutionally relevant genes."

Shippy also cautioned against offering "consensus arrays" as they are "inherently biased toward the state of the field today" and the cytogenetics community is "continually evolving in its practice and learning more about which genes are clinically significant."

As an example of "gene list evolution," Shippy claimed that the ISCA consortium recently presented data that showed that "29 percent of the genes on the initial ISCA gene list, published a few years ago, are now being classified as benign." In addition, "genes once thought to be benign or variants of unknown significance are now considered to be pathogenic," said Shippy.

By "not limiting ourselves a priori to what we believe is significant, cytogeneticists can accelerate the discovery of new findings," he added.

Like all of the other major providers, Shippy said that cancer cytogenetic testing is an area of "significant growth" for Affy.

"Since cancer samples are heterogeneous, a high-density SNP array enables better detection of low-level mosaics and analysis of clonal evolution patterns," he said of the firm's offering.

Illumina is the other major vendor offering a SNP array for use in cancer cytogenetics. But it is unclear if Illumina will launch a new array based on the CCMC design like Agilent and OGT, or go its own way, like Affy and BlueGnome. Company representatives could not comment in time for this publication.

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