Tapping into tissue trove

American, Danish and Swiss forces combine to develop molecular diagnostics platform for large-scale sequence analysis of FFPE tissue samples

Jeffrey Bouley
CAMBRIDGE, Mass.—Teaming up withDanish collaborators at AROS Applied Biotechnology and hospital staffat Aarhus University, along with Swiss pharma giant Roche, U.S.-basedCLC bio is working to develop a solution for large-scale use offormalin fixed, paraffin embedded (FFPE) tissue in molecularanalyses.

The goal of the $5 million project,half of which will be funded by the Danish National AdvancedTechnology Foundation, is to develop a complete platform forselecting appropriate FFPE samples, choosing the optimal sequencingtechnology and subsequently assembling and analyzing thehigh-throughput sequencing data.

Primary application areas for thiswould be molecular diagnostics research and re-analysis ofpreclinical trials where drugs have failed, despite relatively highrates of positive responses.

"For decades, hospitals globally havecollected millions of diagnostic tissue samples and correspondingpatient data, representing a unique biobank," notes Roald Forsberg,director of scientific development at CLC bio. "However, until nowthere hasn't been a high-throughput solution for collecting,sequencing, and analyzing DNA extracted from FFPE tissue samples. Ournew platform will change that and give access to the researchtreasure trove that lies in these huge biobanks."

If the project is successful, manyinstitutions and companies whose research is dependant on genomicsinformation will benefit, adds Dr. Mogens Kruhøffer, chiefscientific officer at AROS Applied Biotechnology and project mangerof the FFPE project, saying, "They will all benefit from havingaccess much wider range of sample material—materials that have beenstored together with information about each specific patient."

That also explains the strong presenceof Danish collaborators in this project, because with regard topathology services in Denmark, there are presently 19 hospital-basedpathology departments that handle virtually all pathology specimensexamined, according to Kruhøffer.

"Not only do all Danishpopulation-based registries have a high degree of completeness, theycan also be efficiently linked by a unique personal 10-digitidentifier, known as a CPR number. Since 1968, CPR numbers have beenassigned to all Danish citizens and residents at birth or immigrationthrough the Civil Registration System," he explains. "Danishpatient administration systems contain more clinical content than isthe norm in Europe, including a clinical data repository withdischarge letters, referrals, laboratory results and notes. Thus, theavailability of FFPE tissues linked to comprehensive clinicalinformation is extraordinarily good."

In most projects that deal withgenomics analysis, scarce access to sample material is often alimiting factor, and very often, projects need to be reduced in sizeor scope because of limited access to sample material, Kruhøffersays.

"FFPE tissue has been collectedroutinely for more than 100 years," he notes. "If you can getaccess to FFPE material, billions of samples around the world whichare typically stored well, the limiting factor of access to tissueswill basically disappear or at least be reduced significantly. Theremay even be sufficient specimens available to investigate very raredisease on a genomic level with sufficient statistical power."

The project is still at a very earlystage, so it is too early to say where the big roadblocks will be,but Kruhøffer says there will definitely be challenges, as there arecurrently methods available for using FFPE, but so far no generallyaccepted method for large-scale use.

"The process of FFPE does somethingto the tissue material, and the challenge is to try to overcomedistortion that formaldehyde creates in the tissues in a way thatwill allow for large-scale use," he says. "There are manydifferent types of distortion and we will look for ways to overcomethat distortion or to compensate for it."

"With personalized medicine, we'reopening the door to a new era where each patient will be treated inthe most effective way for them individually," says StephenHamilton Dutoit, a professor at the Aarhus University Hospital'sInstitute of Pathology. "One of the requirements for doing this isto be able to compare the genome of the individual patient and theirdiseased tissues to a broad range of control samples. Having accessto high-throughput genomic analyses of the vast number of existingarchive FFPE samples will be an invaluable contribution to achievingthis."
 

Jeffrey Bouley

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