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Tapping into tissue trove
CAMBRIDGE, Mass.—Teaming up with Danish collaborators at AROS Applied Biotechnology and hospital staff at Aarhus University, along with Swiss pharma giant Roche, U.S.-based CLC bio is working to develop a solution for large-scale use of formalin fixed, paraffin embedded (FFPE) tissue in molecular analyses.
The goal of the $5 million project, half of which will be funded by the Danish National Advanced Technology Foundation, is to develop a complete platform for selecting appropriate FFPE samples, choosing the optimal sequencing technology and subsequently assembling and analyzing the high- throughput sequencing data.
Primary application areas for this would be molecular diagnostics research and re- analysis of preclinical trials where drugs have failed, despite relatively high rates of positive responses.
"For decades, hospitals globally have collected millions of diagnostic tissue samples and corresponding patient data, representing a unique biobank," notes Roald Forsberg, director of scientific development at CLC bio. "However, until now there hasn't been a high-throughput solution for collecting, sequencing, and analyzing DNA extracted from FFPE tissue samples. Our new platform will change that and give access to the research treasure trove that lies in these huge biobanks."
If the project is successful, many institutions and companies whose research is dependant on genomics information will benefit, adds Dr. Mogens Kruhøffer, chief scientific officer at AROS Applied Biotechnology and project manger of the FFPE project, saying, "They will all benefit from having access much wider range of sample material—materials that have been stored together with information about each specific patient."
That also explains the strong presence of Danish collaborators in this project, because with regard to pathology services in Denmark, there are presently 19 hospital-based pathology departments that handle virtually all pathology specimens examined, according to Kruhøffer.
"Not only do all Danish population- based registries have a high degree of completeness, they can also be efficiently linked by a unique personal 10-digit identifier, known as a CPR number. Since 1968, CPR numbers have been assigned to all Danish citizens and residents at birth or immigration through the Civil Registration System, " he explains. "Danish patient administration systems contain more clinical content than is the norm in Europe, including a clinical data repository with discharge letters, referrals, laboratory results and notes. Thus, the availability of FFPE tissues linked to comprehensive clinical information is extraordinarily good."
In most projects that deal with genomics analysis, scarce access to sample material is often a limiting factor, and very often, projects need to be reduced in size or scope because of limited access to sample material, Kruhøffer says.
"FFPE tissue has been collected routinely for more than 100 years," he notes. "If you can get access to FFPE material, billions of samples around the world which are typically stored well, the limiting factor of access to tissues will basically disappear or at least be reduced significantly. There may even be sufficient specimens available to investigate very rare disease on a genomic level with sufficient statistical power."
The project is still at a very early stage, so it is too early to say where the big roadblocks will be, but Kruhøffer says there will definitely be challenges, as there are currently methods available for using FFPE, but so far no generally accepted method for large-scale use.
"The process of FFPE does something to the tissue material, and the challenge is to try to overcome distortion that formaldehyde creates in the tissues in a way that will allow for large-scale use," he says. "There are many different types of distortion and we will look for ways to overcome that distortion or to compensate for it."
"With personalized medicine, we're opening the door to a new era where each patient will be treated in the most effective way for them individually," says Stephen Hamilton Dutoit, a professor at the Aarhus University Hospital's Institute of Pathology. "One of the requirements for doing this is to be able to compare the genome of the individual patient and their diseased tissues to a broad range of control samples. Having access to high-throughput genomic analyses of the vast number of existing archive FFPE samples will be an invaluable contribution to achieving this."