Nearly 90 percent of all solid tumor samples are fixed in formalin and embedded in paraffin — that's an estimated 1 billion FFPE samples stored throughout the world, says the University of Utah's Joshua Schiffman. And Affymetrix is tapping into that market with its OncoScan FFPE Express 2.0, a new version of the company's already popular assay. The new assay, which the firm announced at the American Association for Cancer Research's annual conference in Orlando, Fla., in April, aims to make analyzing FFPE samples easier and more informative for researchers.
The FFPE process tends to degrade the quality of DNA and makes it more difficult for genomic researchers to get any useful information out of them, especially for older samples. Affymetrix designed the OncoScan assay to overcome those problems. It provides "excellent quality results for genome-wide copy number, loss of heterozygosity, and somatic mutation data," with a very small amount of DNA — about 75 nanograms — required, says Schiffman, who has used the service in a number of studies.
The 2.0 version of the assay, which Affymetrix developed with input from various cancer researchers including those involved in the Stand Up to Cancer initiative, has enhanced coverage of tumor suppressor genes and oncogenes, and, the company says, has added somatic mutations — some 400 of them — in relevant cancer pathways. "The ability to get this type of genomic data from FFPE truly holds enormous implications for both molecular discovery and clinical studies," Schiffman says. The assay also contains more than 330,000 probes, which makes it better than standard CGH in its ability to identify runs of copy-neutral homozygosity, he adds.
Schiffman and his team have done several studies using the Affymetrix assay. Most recently, he analyzed clinically-archived FFPE bone marrow aspirate clots from pediatric leukemia, and discovered unique deletions associated with leukemogenesis. "Similarly, we have analyzed FFPE diagnostic biopsies as old as 15 years from patients who presented with Ewing's sarcoma, a rare pediatric bone tumor," Schiffman says. "We have identified novel areas of chromosomal deletions and amplification that correlate with prognosis in Ewing's sarcoma as well as previously undescribed molecular changes that we believe are related to tumorigenesis." He and his team have also used OncoScan to confirm a micro-deletion syndrome in a patient specimen that was more than 20 years old.
Affymetrix says the OncoScan 2.0 has a 92 percent pass rate with FFPE samples, and a 60-fold dynamic range for copy number change detection. One aspect that has researchers buzzing is the ability to sequence samples that have lain in storage vaults for decades — the company claims to have successfully analyzed samples that were more than 25 years old.
OncoScan FFPE Express 2.0 is in late-stage development at this point, and Affymetrix expects to start offering the service in May. The company is also considering putting the service into the hands of researchers, perhaps by turning it into a kit for purchase.