New York State's Department of Health Clinical Laboratory Evaluation Program last month gave Quest Diagnostics the green light to offer its ClariSure microarray-based comparative genomic-hybridization neonatal test in the state.
The decision made Quest one of three US labs to be approved to perform aCGH testing on neonatal samples collected from patients in New York. The other two labs are Spokane, Wash.-based Signature Genomic Laboratories and the Clinical Cytogenetics Laboratory at the University of Rochester. Both offer testing for prenatal, neonatal, and cancer indications.
Next on Quest's agenda is to submit applications to the New York regulators asking for permission to run CGH tests on prenatal, miscarriage, and oncology samples in a clinical setting, according to a company official.
Charles Strom, medical director of the genetic testing center of Quest Diagnostics' Nichols Institute, told BioArray News this week that, in addition to analyzing neonatal samples, Quest will offer analysis of "prenatal, oncology, and miscarriage [samples] all in the near future."
Quest, whose ClariSure test is based on a bacterial artificial chromosome array, is also considering adopting oligonucleotide array-based platforms sold by companies such as Affymetrix, Agilent Technologies, Illumina, and others.
The ClariSure aCGH test was approved in New York to detect copy-number chromosomal abnormalities implicated in conditions including birth defects, autism spectrum, mental retardation, and other developmental disorders.
Quest initially launched ClariSure in 2007. The platform relies on an array that includes 3,200 BAC clones spaced across the genome with increased density in regions of known syndromic loci. Quest prints the ClariSure platform in-house and makes it available as a laboratory-developed test through its cyto labs in San Juan Capistrano, Calif., and Chantilly, Va.
Each clone on ClariSure is printed in duplicate and a dye-swap is run in each experiment to generate four data points for each spotted clone, a technique that Strom said makes the resulting statistics "extremely sensitive." A ClariSure data-analysis tool has also been designed by Quest's informatics team for use with the platform, Strom said. Results are typically followed up by sequencing or fluorescent in situ hybridization.
According to Strom, Quest decided to make array-based cyto testing available because of the low success rate of traditional cytogenetic assays, like molecular karyotyping. "Our diagnostic armament wasn't doing well. We rarely found the cause of what was going on," he said. "From the early days of using array CGH, the pick up rate was doubled or tripled from standard cytogenetics."
While many competing labs, such as Signature or Baylor College of Medicine, have made oligo-based arrays available in their services over the past two years, Quest has stuck with its BAC platform due to performance and regulatory reasons, Strom said.
"One of the issues in all of the [commercial] platforms is that none of them are [US Food and Drug Administration]-cleared for clinical use," Strom said. "It becomes problematic for labs when they are using products that may be considered devices by FDA in terms of clinical testing," he said. "So, we decided to make our own laboratory-developed test."
Strom acknowledged that there has been a "plethora of advances" in the development of oligo-based platforms for cytogenetic testing. Labs like Quest can now choose from platforms produced by companies like Affy, Agilent, BlueGnome, Illumina, Oxford Gene Technology, and Roche NimbleGen.
While he praised the availability of these platforms, Strom said that they "do not perform as well as BACs for several things," including identifying CNVs or having a good signal-to-noise ratio. He also said that BAC arrays are particularly well suited for use in oncology research and testing, where the copious information provided by an oligo array can cause an analysis headache for the cytogeneticist.
"No one is normal on an oligo array, and so determining the meaning of a particular CNV becomes a matter of interpretation rather than solid data," Strom said. "We believe that oligos will have their place in identifying CNVs, but we have decided to use the gold standard [BAC arrays] until the point that we are happy with the performance of the oligo platforms and there is enough information to make valid clinical interpretations of [the] results."
That said, Quest believes that every large cyto lab should have access to both BAC and oligo-based platforms. Strom said that Quest is now taking a look at the commercial platforms and will soon decide on which one is best suited for its purposes.
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Quest's rivals in the array-based cyto testing market include labs like Signature, Laboratory Corporation of America, Baylor, and CombiMatrix Molecular Diagnostics, whose CEO Mansoor Mohammed is a Quest alum.
To date, few of these labs have put significant resources into sales and marketing, but they have seen a growing demand for their services. Signature, for example, has run 30,000 arrays to date since it began offering its services in 2004. Baylor has run 20,000. And even LabCorp, which began offering cyto services on the Affymetrix platform last year, has run 5,000 samples to date.
Strom attributed this growth to the demand for better cytogenetic tools. "There was so much pent-up demand for CGH that it took off without much sales and marketing," Strom said. "Sales and marketing can be involved in these decisions, but insurance companies typically determine where tests get sent," he said. In that way, the consumers who are requesting the tests often have no choice in whether their samples go to Signature or to Quest.
Strom said that he does not consider Signature or Baylor to be rivals, though they offer similar services. "They are not competitors; they are collaborators," Strom said. "My chief concern is that everybody in the US can get this test. Sales and marketing people may compete for market share, but that's not my concern."
According to Strom, there is enough demand for array-based cyto testing for "everybody to make a living," but the greatest obstacle the field faces is standardization. "Today, you might get different results depending on where you send your samples," Strom said. "That is not because people are doing a bad job; they are just using different platforms."
He said because all arrays being used in various lab services are of different designs, it slows the adoption of array-based cytogenetic testing in the marketplace. "The best case scenario is when tests are completely objective," Strom said. "When a computer can make a call and it's the same whether the sample is run in Timbuktu or Minnesota, it will be ideal. That is not the case with arrays today."