BlueGnome, a seller of arrays and other consumables to the cytogenetic testing market, this week launched a hematology-themed array, the first in what the company said will become a new menu of next-generation chips.
Graham Snudden, co-founder and vice president of engineering of the Cambridge, UK-based firm, told BioArray News this week that the company has validated and begun shipping its hematology array for the investigation of the most common hematological malignancies.
The chip is being made available in BlueGnome’s new CytoChip Focus format, which Snudden said includes more extensive content replication, more advanced bioinformatics tools, more sophisticated controls on the chip, and the removal of copy number polymorphism clones that were available on the company’s older offering, the CytoChip.
The BlueGnome Focus hematology array version 1.0 investigates copy number imbalance in 50 regions of known clinical significance and larger scale alterations in the backbone. BlueGnome expects to launch a second version with additional coverage sometime next year.
While intended only for research use, Snudden made it clear that the Focus-format arrays could be used together with contemporary cytogenetics techniques, such as G-band karyotyping and fluorescent in situ hybridization, in a clinical setting. Both the CytoChip Focus and CytoChip are bacterial artificial chromosome arrays designed for use in comparative genomic hybridization experiments.
“We would argue that results from the Focus format are more suitable for diagnostic applications because the array only delivers results which are informative in a given clinical context,” Snudden said. “A major limitation of many arrays is that they produce too much data because new data of unknown significance can complicate, rather than inform, the management of the patient.”
According to Snudden, BlueGnome’s CytoChip is currently used by some European clinics to investigate hematology samples. “Talking to these laboratories, they request higher sensitivity in mosaic cell populations, targeting of regions known to be associated with hematological malignancies, and a removal of CNVs, some constitutional regions, and other information which is not relevant to their investigation,” he said. “The result was the Focus format.”
BlueGnome’s latest product launch has several competitive angles, said Snudden. From one perspective, the company is seeking to complement or replace older cytogenetic methods that cannot provide cytogeneticists with certain answers.
For example, Snudden pointed out that both FISH and G-banding require sample cells to be cultured, introducing the possibility that differential growth rates between malignant and healthy cells could result in certain malignancies being underestimated or missed by the cytogeneticist.
“A major limitation of many arrays is that they produce too much data, because new data of unknown significance can complicate, rather than inform, the management of the patient.”
Beyond reaching cytogeneticists using these methods, BlueGnome is competing against firms that also sell chips for CGH, including PerkinElmer, Affymetrix, Oxford Gene Technology, and Agilent Technologies. From a broader perspective, other players in the field include service labs such as CombiMatrix Molecular Diagnostics and Signature Genomic Laboratories.
While most array companies in the market offer general research tools, such as Affymetrix’s Cytogenetic Solution or PerkinElmer’s SpectralChip, some have narrowed in on those researching and diagnosing leukemias and lymphomas using array CGH.
Irvine, Calif.-based CombiMatrix Molecular Diagnostics, for example, recently launched a BAC array-based test for chronic lymphocytic leukemia. The test, called HemeScan, is designed to detect all of the known recurrent genomic abnormalities associated with prognosis in CLL while providing a global view of the tumor genome.
The bulk of BlueGnome’s business, though, is in Europe, and Snudden said that the company is not looking to go head-to-head against CMDX’s test, though it has begun branching out into the North American market over the past year (see BAN 9/11/2007).
“We are a product company and do not currently offer a service capability,” he said. “In that sense we would consider any other supplier of microarrays, FISH probes, and associated software and consumables a potential competitor.”
Snudden said that the company’s arrays are open-platform and are compatible with all instrumentation developed for use with two-channel, fluorescently labeled microarrays. He also acknowledged that some rivals use oligo arrays, rather than BAC arrays, in their CGH products.
“The choice between BAC versus oligo is primarily related to the manufacturing capability of the vendor,” Snudden said. “The literature continues to show a broadly similar performance between the two approaches both in terms of the size and frequency of pathogenic imbalances detected and the overall diagnostic yield of the various platforms,” he added.
Snudden claimed that BlueGnome has recently completed a validation study of the CytoChip Focus hematology array. However, he declined to name all the centers involved in validating the array and said that the company is still considering publishing the study.
However, Eigil Kjeldsen, the head of cancer cytogenetics at Aarhus University Hospital in Denmark, is one of the investigators involved in the validation study, according to a statement issued by BlueGnome this week.
Kjeldsen said this week that his lab provides risk stratification and treatment recommendation for pediatric and adult leukemia patients. Kjeldsen told BioArray News that the hospital has been using BlueGnome arrays in conjunction with FISH analysis and routine G-banding in its cases since early 2007.
He said that, above all, the array was introduced to make up for the shortcomings of the other technologies. “One of the major problems in leukemia is that cells are slow to divide and it can be very cumbersome to study these chromosomes,” he said. ”No matter how good your analysis is,” he added, “it is impossible to see translocation between chromosome 12 and 21.
“The big difference between CGH and G-banding and FISH, is that G-banding and FISH show you one cell; array CGH gives you general overview of all cells inside your sample,” he said. “That way, if you have more than 20 or 30 abnormal cells, you would be able to detect genomic imbalances in a sample.”
Kjeldsen cited ease of use and lower cost when describing why he chose to use BlueGnome over other available CGH platforms. Though he is satisfied with the arrays’ performance, his lab will continue to use BlueGnome’s chip with the older technologies.
“We put the CGH on top and we go back and validate the findings,” he explained. “Our main goal is that it is a supportive method giving higher resolution as opposed to our other methods.”
He said he was aware of the discussion about whether oligos or BACs were better suited for cytogenetics applications, but said that the resolution of the BlueGnome chip is fine, considering the needs of his lab.