Covance, ISB form brain tumor partnership

Researchers to study the genetic differences occurring within glioblastoma multiforme

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SEATTLE—Covance's genomics laboratory located here has struck a collaboration with the Institute for Systems Biology (ISB) to study brain tumors, one of the most deadly forms of human cancer.

In the collaboration, researchers will study the genetic differences that lurk within glioblastoma multiforme (GBM) and find molecular targets that may enable researchers to select the right drug for the right patient. Financial terms of the collaboration were not disclosed.

GBM has an average survival time of a little more than one year after diagnosis, a fact that has not changed in more than a hundred years. According to Thomas Turi, vice president of science and technology for Covance Discovery and Translational Services, considerable efforts have been applied to unravel the complicated genetic background of GBM.

"The Cancer Genome Atlas (TCGA) network initiated by the National Institutes of Health (NIH) chose GBM as one of the first cancer types for its pilot study to characterize genomic abnormalities using a variety of technologies including DNA microarrays and targeted Sanger sequencing approaches," he says. "By analyzing more than 200 GBM patients, the TCGA has laid the groundwork for systematic integration of genetic variations, molecular profiles and clinical phenotypes."

This new research project will combine the companies' capabilities in genomics, with Covance providing assay and sequencing services. Covance will generate all the data required for this project and will participate in analysis along with scientists from the ISB, which is also based in Seattle.

Having run more than 450,000 samples to date, Covance's genomics laboratory provides end-to-end services for genomics-based development research and has demonstrated particular expertise in next-generation sequencing (NGS), which will be used to provide researchers an important dataset to investigate tumor heterogeneity and find targets for patient stratification and/or therapeutics.

Covance arrived in Seattle in July 2009, when it bought the gene expression lab that was part of Merck & Co. Inc.'s Rosetta Inpharmatics unit. The collaboration will be the first time that Covance and ISB have worked together directly, though there is a connection dating to when the lab was part of Rosetta Inpharmatics, of which Leroy Hood was a co-founder. In its more than 10-year history, several scientists from Covance Genomic Laboratory (CGL) have either worked directly or indirectly with Hood and the ISB on various projects.

"Collaborating with Covance will help us better understand the disease of glioblastoma multiforme biology," says Hood, president of the ISB. "We know Covance's experience in genomics and next-generation sequencing will give us an unprecedented level of high-quality data."
According to Turi, the ISB proved to be a perfect fit in this effort because of its work in developing innovative technologies and computational tools required for understanding biological complexity.

"Given the complex nature of this disease, the ISB is an obvious partner, as the data generated will be varied and complicated, requiring the expertise that only the ISB can bring," he says. "To facilitate greater collaboration and communications, the ISB will be moving into the same facility where CGL is located in Seattle."

Turi explains that NGS has "revolutionized the field of genomics by allowing investigation of the genomic aberrations associated with different cancers, or any other disease, at an unprecedented level."

"Being digital in nature and due to its larger dynamic range compared to microarrays, this technology helps in the identification of novel genetic alterations, non-coding RNAs and alternative splicing, in addition to gene expression associated with various diseases," he continues. "As more data becomes available, there is a growing need in the industry to develop automated pipelines to integrate and mine complex datasets for better understanding of the diseases for drug development."

Moreover, Turi notes that these studies will provide new insights and associated new discoveries will lead to entirely new approaches to treat brain cancer.

"Integration of various datasets to look at all of the important aspects of GBM etiology:  mutations, gene expression, promoter analysis, etc., will allow us to define how each of these plays a role in regulating different networks. For example, by mining these networks, we will be able to identify gene signatures associated with different cell sub-types associated with GBM," he says. "As GBM is a highly heterogeneous disease, this information will be very useful to identify and isolate different types of tumor-initiating cells from patients and target them for therapeutics. In the future, these biomarkers can be used in the clinic by physicians for personalized medicine."

Once finished, the results of the analysis along with the raw data will be released to public databases and submitted for publication in a peer-reviewed scientific journal.

"This information will be available to the entire scientific community to further enhance our understanding of this condition and to help make a difference in the lives of people suffering with this terrible disease," Turi concludes.



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