Releasing a new gene expression-profiling product, Illumina hopes to get its foot in the door of a potentially huge market fraught with notoriously difficult obstacles — formalin-fixed paraffin-embedded tissue analysis.
Illumina’s product, known as the cDNA-mediated annealing, selection, extension and ligation assay — or DASL — will sell for “maybe $100” per assay, said Illumina spokesperson Bill Craumer. There are as many as 400 million FFPE samples in the United States, according to Craumer, who said the company would “be real happy getting maybe 1 percent of those samples assayed.”
If these numbers are any guide — and it’s extremely difficult to find an accurate number of these kinds of samples floating in pathology labs and oncology practices nationwide — Illumina could soon begin excavating its $400 million portion of a potentially $40 billion market.
But that might be easier said than done.
Institutions like cancer centers and biobanks store tissue samples for patients whose treatment outcomes are known, and whose disease progression has been tracked. The resulting mass of information could be a potential goldmine of biomarker data for drug makers and disease researchers.
The specimens, some of which date to before the Human Genome Project, can be useful in identifying biomarkers important in drug discovery, diagnostics, and in finding new uses for existing drugs, according to Carolyn Compton, pathologist-in-chief at the McGill University Health Center.
Sitting in refrigerators and room-temperature storage shelves across the nation, many of these samples have degraded to the point where their RNA comprises fragments too small to be read using conventional analytical means.
But this is hardly uninhabited. About one year ago, Affymetrix and Arcturus together introduced their gene-expression products for FFPE samples — Affy’s GeneChip Human Genome X3P array and Arcturus’ Paradise RNA extraction and amplification reagents.
If the two methods compete purely by price, Illumina’s DASL may have the upper hand. Affy generally sells the X3P for about the same price as its other human genome arrays, while the Paradise reagents cost approximately $200 per sample, said Greg Milosevich, Arcturus vice president for worldwide sales. However, Paradise includes RNA isolation reagents, which means that DASL users will have to use their own methods.
“There are over 400 cancer centers and banks across the country that are utilizing [Arcturus’] product now,” including Fox Chase, Allegheny General Hospital, and MD Anderson, said Milosevich.
Milosevich declined to disclose the number of Paradise products sold since last year, and he was unable to estimate the size of the FFPE-tissue gene-expression market. However, like Illumina’s Craumer, he estimates that there is an enormous number of samples nationwide that are inaccessible by ordinary methods — about 100 million of them by his count. “We see this product as having a fairly attractive growth potential in the market,” said Milosevich.
Is There a Market?
But can either Illumina or Arcturus-Affy deliver what the market really needs — a product that works? So far, the measurement of gene expression in FFPE-tissue products “is kind of in its beginnings — ‘infancy’ is too strong a word,” said Craig Allred, a professor of pathology at the Breast Center of Baylor College of Medicine. “People have been trying to do it for five years,” he said. “I am only aware of two publications that have actually been successful in doing it, so there are some products out there and folks are starting to use them. It’s just not as easy as it sounds,” he added.
In two unrelated projects, Allred’s lab is using a chimeric method — Ambion Optimum for FFPE RNA isolation, Arcturus Paradise for amplification, and Affy X3P for detection — to achieve “reasonable results,” he said. “The only stuff I’m aware of that’s been published is the [Arcturus] Paradise” reagents in combination with specialty Agilent or Affy chips, said Allred.
The Arcturus-Affy system is “very, very expensive — and it works,” said Allred. “But you have to have really optimum starting material. It turns out that not all paraffin blocks are created equal,” he said. Compounding this problem, both the Arcturus and Affy products use “poly-A-dependent approaches,” he said. “It presents special problems, and I haven’t seen other strategies to circumvent that,” he added.
Is there room for two FFPE-tissue specialty products in this market? Asked whether DASL will compete for the same customers, Milosevich said no. “Our system is designed to look at the whole genome of an organism,” whereas DASL can interrogate a particular set of genes, he said. In addition, customers will probably choose the system that complements a gene-expression platform to which they have access, he said.
Each Illumina DASL assay can measure customizable sets of a maximum of 512 transcripts per experiment, as opposed to X3P’s 44,000, according to literature from both companies.
Can sensitivity make up the difference? While the majority of the transcripts on Affy’s GeneChip Human Genome X3P are interrogated by one complementary sequence each, Illumina is hoping that its three sequence-specific probes per transcript will add enough sensitivity to differentiate DASL.